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Embryonic Stem Cells | stemcells.nih.gov

By adminOctober 9, 2016Embryonic Stem Cells

by Junying Yu* and James A. Thomson**

Human embryonic stem (ES) cells capture the imagination because they are immortal and have an almost unlimited developmental potential (Fig. 1.1: How hESCs are derived). After many months of growth in culture dishes, these remarkable cells maintain the ability to form cells ranging from muscle to nerve to bloodpotentially any cell type that makes up the body. The proliferative and developmental potential of human ES cells promises an essentially unlimited supply of specific cell types for basic research and for transplantation therapies for diseases ranging from heart disease to Parkinson's disease to leukemia. Here we discuss the origin and properties of human ES cells, their implications for basic research and human medicine, and recent research progress since August 2001, when President George W. Bush allowed federal funding of this research for the first time. A previous report discussed progress prior to June 17, 2001 (/info/scireport/.)

Figure 1.1. How Human Embryonic Stem Cells are Derived.

( 2006 Terese Winslow)

Embryonic stem cells are derived from embryos at a developmental stage before the time that implantation would normally occur in the uterus. Fertilization normally occurs in the oviduct, and during the next few days, a series of cleavage divisions occur as the embryo travels down the oviduct and into the uterus. Each of the cells (blastomeres) of these cleavage-stage embryos are undifferentiated, i.e. they do not look or act like the specialized cells of the adult, and the blastomeres are not yet committed to becoming any particular type of differentiated cell. Indeed, each of these blastomeres has the potential to give rise to any cell of the body. The first differentiation event in humans occurs at approximately five days of development, when an outer layer of cells committed to becoming part of the placenta (the trophectoderm) separates from the inner cell mass (ICM). The ICM cells have the potential to generate any cell type of the body, but after implantation, they are quickly depleted as they differentiate to other cell types with more limited developmental potential. However, if the ICM is removed from its normal embryonic environment and cultured under appropriate conditions, the ICM-derived cells can continue to proliferate and replicate themselves indefinitely and still maintain the developmental potential to form any cell type of the body (quot;pluripotencyquot;; see Fig. 1.2: Characteristics of ESCs). These pluripotent, ICM-derived cells are ES cells.

Figure 1.2.Characteristics of Embryonic Stem Cells.

( 2006 Terese Winslow)

The derivation of mouse ES cells was first reported in 1981,1,2 but it was not until 1998 that derivation of human ES cell lines was first reported.3 Why did it take such a long time to extend the mouse results to humans? Human ES cell lines are derived from embryos produced by in vitro fertilization (IVF), a process in which oocytes and sperm are placed together to allow fertilization to take place in a culture dish. Clinics use this method to treat certain types of infertility, and sometimes, during the course of these treatments, IVF embryos are produced that are no longer needed by the couples for producing children. Currently, there are nearly 400,000 IVF-produced embryos in frozen storage in the United States alone,4 most of which will be used to treat infertility, but some of which (~2.8%) are destined to be discarded. IVF-produced embryos that would otherwise have been discarded were the sources of the human ES cell lines derived prior to President Bush's policy decision of August 2001. These human ES cell lines are now currently eligible for federal funding. Although attempts to derive human ES cells were made as early as the 1980s, culture media for human embryos produced by IVF were suboptimal. Thus, it was difficult to culture single-cell fertilized embryos long enough to obtain healthy blastocysts for the derivation of ES cell lines. Also, species-specific differences between mice and humans meant that experience with mouse ES cells was not completely applicable to the derivation of human ES cells. In the 1990s, ES cell lines from two non-human primates, the rhesus monkey5 and the common marmoset,6 were derived, and these offered closer models for the derivation of human ES cells. Experience with non-human primate ES cell lines and improvements in culture medium for human IVF-produced embryos led rapidly to the derivation of human ES cell lines in 1998.3

Because ES cells can proliferate without limit and can contribute to any cell type, human ES cells offer an unprecedented access to tissues from the human body. They will support basic research on the differentiation and function of human tissues and provide material for testing that may improve the safety and efficacy of human drugs (Figure 1.3: Promise of SC Research).7,8 For example, new drugs are not generally tested on human heart cells because no human heart cell lines exist. Instead, researchers rely on animal models. Because of important species-specific differences between animal and human hearts, however, drugs that are toxic to the human heart have occasionally entered clinical trials, sometimes resulting in death. Human ES cell-derived heart cells may be extremely valuable in identifying such drugs before they are used in clinical trials, thereby accelerating the drug discovery process and leading to safer and more effective treatments.911 Such testing will not be limited to heart cells, but to any type of human cell that is difficult to obtain by other sources.

Figure 1.3: The Promise of Stem Cell Research.

( 2006 Terese Winslow)

Human ES cells also have the potential to provide an unlimited amount of tissue for transplantation therapies to treat a wide range of degenerative diseases. Some important human diseases are caused by the death or dysfunction of one or a few cell types, e.g., insulin-producing cells in diabetes or dopaminergic neurons in Parkinson's disease. The replacement of these cells could offer a lifelong treatment for these disorders. However, there are a number of challenges to develop human ES cell-based transplantation therapies, and many years of basic research will be required before such therapies can be used to treat patients. Indeed, basic research enabled by human ES cells is likely to impact human health in ways unrelated to transplantation medicine. This impact is likely to begin well before the widespread use of ES cells in transplantation and ultimately could have a more profound long-term effect on human medicine. Since August 2001, improvements in culture of human ES cells, coupled with recent insights into the nature of pluripotency, genetic manipulation of human ES cells, and differentiation, have expanded the possibilities for these unique cells.

Mouse ES cells and human ES cells were both originally derived and grown on a layer of mouse fibroblasts (called quot;feeder cellsquot;) in the presence of bovine serum. However, the factors that sustain the growth of these two cell types appear to be distinct. The addition of the cytokine, leukemia inhibitory factor (LIF), to serum-containing medium allows mouse ES cells to proliferate in the absence of feeder cells. LIF modulates mouse ES cells through the activation of STAT3 (signal transducers and activators of transcription) protein. In serum-free culture, however, LIF alone is insufficient to prevent mouse ES cells from differentiating into neural cells. Recently, Ying et al. reported that the combination of bone morphogenetic proteins (BMPs) and LIF is sufficient to support the self-renewal of mouse ES cells.12 The effects of BMPs on mouse ES cells involve induction of inhibitor of differentiation (Id) proteins, and inhibition of extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinases (MAPK).12,13 However, LIF in the presence of serum is not sufficient to promote the self-renewal of human ES cells,3 and the LIF/STAT3 pathway appears to be inactive in undifferentiated human ES cells.14,15 Also, the addition of BMPs to human ES cells in conditions that would otherwise support ES cells leads to the rapid differentiation of human ES cells.16,17

Several groups have attempted to define growth factors that sustain human ES cells and have attempted to identify culture conditions that reduce the exposure of human ES cells to non human animal products. One important growth factor, bFGF, allows the use of a serum replacement to sustain human ES cells in the presence of fibroblasts, and this medium allowed the clonal growth of human ES cells.18 A quot;feeder-freequot; human ES cell culture system has been developed, in which human ES cells are grown on a protein matrix (mouse Matrigel or Laminin) in a bFGF-containing medium that is previously quot;conditionedquot; by co-culture with fibroblasts.19 Although this culture system eliminates direct contact of human ES cells with the fibroblasts, it does not remove the potential for mouse pathogens being introduced into the culture via the fibroblasts. Several different sources of human feeder cells have been found to support the culture of human ES cells, thus removing the possibility of pathogen transfer from mice to humans.2023 However, the possibility of pathogen transfer from human to human in these culture systems still remains. More work is still needed to develop a culture system that eliminates the use of fibroblasts entirely, which would also decrease much of the variability associated with the current culture of human ES cells. Sato et al. reported that activation of the Wnt pathway by 6-bromoindirubin3'-oxime (BIO) promotes the self-renewal of ES cells in the presence of bFGF, Matrigel, and a proprietary serum replacement product.24 Amit et al. reported that bFGF, TGF, and LIF could support some human ES cell lines in the absence of feeders.25 Although there are some questions about how well these new culture conditions will work for different human ES cell lines, there is now reason to believe that defined culture conditions for human ES cells, which reduce the potential for contamination by pathogens, will soon be achieved*.

Once a set of defined culture conditions is established for the derivation and culture of human ES cells, challenges to improve the medium will still remain. For example, the cloning efficiency of human ES cellsthe ability of a single human ES cell to proliferate and become a colonyis very low (typically less than 1%) compared to that of mouse ES cells. Another difficulty is the potential for accumulation of genetic and epigenetic changes over prolonged periods of culture. For example, karyotypic changes have been observed in several human ES cell lines after prolonged culture, and the rate at which these changes dominate a culture may depend on the culture method.26,27 The status of imprinted (epigenetically modified) genes and the stability of imprinting in various culture conditions remain completely unstudied in human ES cells**. The status of imprinted genes can clearly change with culture conditions in other cell types.28,29 These changes present potential problems if human ES cells are to be used in cell replacement therapy, and optimizing medium to reduce the rate at which genetic and epigenetic changes accumulate in culture represents a long-term endeavor. The ideal human ES cell medium, then, (a) would be cost-effective and easy to use so that many more investigators can use human ES cells as a research tool; (b) would be composed entirely of defined components not of animal origin; (c) would allow cell growth at clonal densities; and (d) would minimize the rate at which genetic and epigenetic changes accumulate in culture. Such a medium will be a challenge to develop and will most likely be achieved through a series of incremental improvements over a period of years.

Among all the newly derived human ES cell lines, twelve lines have gained the most attention. In March 2004, a South Korean group reported the first derivation of a human ES cell line (SCNT-hES-1) using the technique of somatic cell nuclear transfer (SCNT). Human somatic nuclei were transferred into human oocytes (nuclear transfer), which previously had been stripped of their own genetic material, and the resultant nuclear transfer products were cultured in vitro to the blastocyst stage for ES cell derivation.30*** Because the ES cells derived through nuclear transfer contain the same genetic material as that of the nuclear donor, the intent of the procedure is that the differentiated derivatives would not be rejected by the donor's immune system if used in transplantation therapy. More recently, the same group reported the derivation of eleven more human SCNT-ES cell lines*** with markedly improved efficiency (16.8 oocytes/line vs. 242 oocytes/line in their previous report).31*** However, given the abnormalities frequently observed in cloned animals, and the costs involved, it is not clear how useful this procedure will be in clinical applications. Also, for some autoimmune diseases, such as type I diabetes, merely providing genetically-matched tissue will be insufficient to prevent immune rejection.

Additionally, new human ES cell lines were established from embryos with genetic disorders, which were detected during the practice of preimplantation genetic diagnosis (PGD). These new cell lines may provide an excellent in vitro model for studies on the effects that the genetic mutations have on cell proliferation and differentiation.32

* Editor's note: Papers published since this writing report defined culture conditions for human embryonic stem cells. See Ludwig et al., Nat. Biotech 24: 185187, 2006; and Lu et al., PNAS 103:56885693, 2006.08.14.

** Editor's note: Papers published since the time this chapter was written address this: see Maitra et al., Nature Genetics 37, 10991103, 2005; and Rugg-Gunn et al., Nature Genetics 37:585587, 2005.

*** Editor's note: Both papers referenced in 30 and 31 were later retracted: see Science 20 Jan 2006; Vol. 311. No. 5759, p. 335.

To date, more than 120 human ES cell lines have been established worldwide,33* 67 of which are included in the National Institutes of Health (NIH) Registry. As of this writing, 21 cell lines are currently available for distribution, all of which have been exposed to animal products during their derivation. Although it has been eight years since the initial derivation of human ES cells, it is an open question as to the extent that independent human ES cell lines differ from one another. At the very least, the limited number of cell lines cannot represent a reasonable sampling of the genetic diversity of different ethnic groups in the United States, and this has consequences for drug testing, as adverse reactions to drugs often reflect a complex genetic component. Once defined culture conditions are well established for human ES cells, there will be an even more compelling need to derive additional cell lines.

* Editor's note: One recent report now estimates 414 hESC lines, see Guhr et al., http://www.StemCells.com early online version for June 15, 2006: quot;Current State of Human Embryonic Stem Cell Research: An Overview of Cell Lines and their Usage in Experimental Work.quot;

The ability of ES cells to develop into all cell types of the body has fascinated scientists for years, yet remarkably little is known about factors that make one cell pluripotent and another more restricted in its developmental potential. The transcription factor Oct4 has been used as a key marker for ES cells and for the pluripotent cells of the intact embryo, and its expression must be maintained at a critical level for ES cells to remain undifferentiated.34 The Oct4 protein itself, however, is insufficient to maintain ES cells in the undifferentiated state. Recently, two groups identified another transcription factor, Nanog, that is essential for the maintenance of the undifferentiated state of mouse ES cells.35,36 The expression of Nanog decreased rapidly as mouse ES cells differentiated, and when its expression level was maintained by a constitutive promoter, mouse ES cells could remain undifferentiated and proliferate in the absence of either LIF or BMP in serum-free medium.12 Nanog is also expressed in human ES cells, though at a much lower level compared to that of Oct4, and its function in human ES cells has yet to be examined.

By comparing gene expression patterns between different ES cell lines and between ES cells and other cell types such as adult stem cells and differentiated cells, genes that are enriched in the ES cells have been identified. Using this approach, Esg-1, an uncharacterized ES cell-specific gene, was found to be exclusively associated with pluripotency in the mouse.37 Sperger et al. identified 895 genes that are expressed at significantly higher levels in human ES cells and embryonic carcinoma cell lines, the malignant counterparts to ES cells.38 Sato et al. identified a set of 918 genes enriched in undifferentiated human ES cells compared with their differentiated counterparts; many of these genes were shared by mouse ES cells.39 Another group, however, found 92 genes, including Oct4 and Nanog, enriched in six different human ES cell lines, which showed limited overlap with those in mouse ES cell lines.40 Care must be taken to interpret these data, and the considerable differences in the results may arise from the cell lines used in the experiments, methods to prepare and maintain the cells, and the specific methods used to profile gene expression.

Since establishing human ES cells in 1998, scientists have developed genetic manipulation techniques to determine the function of particular genes, to direct the differentiation of human ES cells towards specific cell types, or to tag an ES cell derivative with a certain marker gene. Several approaches have been developed to introduce genetic elements randomly into the human ES cell genome, including electroporation, transfection by lipid-based reagents, and lentiviral vectors.4144 However, homologous recombination, a method in which a specific gene inside the ES cells is modified with an artificially introduced DNA molecule, is an even more precise method of genetic engineering that can modify a gene in a defined way at a specific locus. While this technology is routinely used in mouse ES cells, it has recently been successfully developed in human ES cells (See chapter 4: Genetically Modified Stem Cells), thus opening new doors for using ES cells as vehicles for gene therapy and for creating in vitro models of human genetic disorders such as Lesch-Nyhan disease.45,46 Another method to test the function of a gene is to use RNA interference (RNAi) to decrease the expression of a gene of interest (see Figure 1.4: RNA interference). In RNAi, small pieces of double-stranded RNA (siRNA; small interfering RNA) are either chemically synthesized and introduced directly into cells, or expressed from DNA vectors. Once inside the cells, the siRNA can lead to the degradation of the messenger RNA (mRNA), which contains the exact sequence as that of the siRNA. mRNA is the product of DNA transcription and normally can be translated into proteins. RNAi can work efficiently in somatic cells, and there has been some progress in applying this technology to human ES cells.4749

Figure 1.4. How RNAi Can Be Used To Modify Stem Cells.

( 2006 Terese Winslow)

The pluripotency of ES cells suggests possible widespread uses for these cells and their derivatives. The ES cell-derived cells can potentially be used to replace or restore tissues that have been damaged by disease or injury, such as diabetes, heart attacks, Parkinson's disease or spinal cord injury. The recent developments in these particular areas are discussed in detail in other chapters, and Table 1 summarizes recent publications in the differentiation of specific cell lineages.

The differentiation of ES cells also provides model systems to study early events in human development. Because of possible harm to the resulting child, it is not ethically acceptable to experimentally manipulate the postimplantation human embryo. Therefore, most of what is known about the mechanisms of early human embryology and human development, especially in the early postimplantation period, is based on histological sections of a limited number of human embryos and on analogy to the experimental embryology of the mouse. However, human and mouse embryos differ significantly, particularly in the formation, structure, and function of the fetal membranes and placenta, and the formation of an embryonic disc instead of an egg cylinder.5052 For example, the mouse yolk sac is a well-vascularized, robust, extraembryonic organ throughout gestation that provides important nutrient exchange functions. In humans, the yolk sac also serves important early functions, including the initiation of hematopoiesis, but it becomes essentially a vestigial structure at later times or stages in gestation. Similarly, there are dramatic differences between mouse and human placentas, both in structure and function. Thus, mice can serve in a limited capacity as a model system for understanding the developmental events that support the initiation and maintenance of human pregnancy. Human ES cell lines thus provide an important new in vitro model that will improve our understanding of the differentiation of human tissues, and thus provide important insights into processes such as infertility, pregnancy loss, and birth defects.

Human ES cells are already contributing to the study of development. For example, it is now possible to direct human ES cells to differentiate efficiently to trophoblast, the outer layer of the placenta that mediates implantation and connects the conceptus to the uterus.17,53 Another use of human ES cells is for the study of germ cell development. Cells resembling both oocytes and sperm have been successfully derived from mouse ES cells in vitro.5456 Recently, human ES cells have also been observed to differentiate into cells expressing genes characteristic of germ cells.57 Thus it may also be possible to derive oocytes and sperm from human ES cells, allowing the detailed study of human gametogenesis for the first time. Moreover, human ES cell studies are not limited to early differentiation, but are increasingly being used to understand the differentiation and functions of many human tissues, including neural, cardiac, vascular, pancreatic, hepatic, and bone (see Table 1). Moreover, transplantation of ES-derived cells has offered promising results in animal models.5867

Although scientists have gained more insights into the biology of human ES cells since 2001, many key questions remain to be addressed before the full potential of these unique cells can be realized. It is surprising, for example, that mouse and human ES cells appear to be so different with respect to the molecules that mediate their self-renewal, and perhaps even in their developmental potentials. BMPs, for example, in combination with LIF, promote the self-renewal of mouse ES cells. But in conditions that would otherwise support undifferentiated proliferation, BMPs cause rapid differentiation of human ES cells. Also, human ES cells differentiate quite readily to trophoblast, whereas mouse ES cells do so poorly, if at all. One would expect that at some level, the basic molecular mechanisms that control pluripotency would be conserved, and indeed, human and mouse ES cells share the expression of many key genes. Yet we remain remarkably ignorant about the molecular mechanisms that control pluripotency, and the nature of this remarkable cellular state has become one of the central questions of developmental biology. Of course, the other great challenge will be to continue to unravel the factors that control the differentiation of human ES cells to specific lineages, so that ES cells can fulfill their tremendous promise in basic human biology, drug screening, and transplantation medicine.

We thank Lynn Schmidt, Barbara Lewis, Sangyoon Han and Deborah J. Faupel for proofreading this report.

Notes:

* Genetics and Biotechnology Building, Madison, WI 53706, Email: jyu@primate.wisc.edu.

** John D. MacArthur Professor, Department of Anatomy, University of WisconsinMadison Medical School, The Genome Center of Wisconsin, and The Wisconsin National Primate Research Center, Madison, WI 53715, Email: thomson@primate.wisc.edu.

Introduction|Table of Contents|Chapter 2

Originally posted here:
Embryonic Stem Cells | stemcells.nih.gov

Induced Pluripotent Stem Cell Initiative | California’s …

By adminOctober 7, 2016Induced Pluripotent Stem Cells

The Induced Pluripotent Stem Cell (iPSC) Initiative is a major effort from CIRM to create a collection of stem cells developed from thousands of individuals.

CIRM is creating the iPSC bank so that scientists can use the cells, either in a petri dish or transplanted into animals, to study how disease develops and progresses and develop and test new drugs or other therapies. The iPSC bank is now open and cell lines are available at catalog.coriell.org/CIRM.

The large size of the collection will provide researchers with a powerful tool for studying genetic variation between individuals, helping scientists understand how disease and treatment may vary in a diverse population like Californias.

Outside Stem Cell Lines

The CIRM iPSC Repository is now accepting up to 300 human pluripotent stem cell lines (including human Embryonic Stem Cells or human induced Pluripotent Stem Cells) from outside laboratories. Submitted lines can be expanded, at no cost to the investigator, for storage and distribution in the Repository.

The deadline for cell line submission is October 12, 2016. For more information about this opportunity and for submission criteria, see attached document below:

What is the iPSC Initative? How does it work? Why iPS cells? Who is generating the cells? Which diseases will be represented? How many samples are being collected for each condition?

What is the iPSC Initiative? The Human Induced Pluripotent Stem Cell (hiPSC) Initiative is one of the California stem cell agencys major efforts to provide valuable resources to the research community. The goal is to create a bank of high quality stem cell lines developed from thousands of individuals for use in research.

How does it work? Blood or skin samples collected from approximately 3,000 individuals will be turned into stem cell lines. These lines will be made available to researchers throughout California and around the world.

Why iPS cells? iPS cells are generated from cells easily obtained from living humans, i.e. blood or a small piece of skin; they have unlimited expansion potential in the petri dish, so huge numbers of cells can be generated for research studies or drug development; and they can be coaxed into the types of cells affected in various diseases, such as heart or brain disorders. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease but cannot otherwise be easily obtained in large quantities from them.

Who is generating the cells? Seven clinician scientists from four California institutions recruit tissue donors who suffer from one of the included diseases or are healthy controls. Some blood or a small piece of skin is collected from those donors, and these samples are shipped to the company Cellular Dynamics International (CDI). CDI generates iPS cells from the samples, and then transfers the iPS cells to the Coriell Institute for Biomedical Research. Coriell operates a cell bank that will distribute the iPS cells to interested researchers at academic and other non-profit institutions, and also to pharmaceutical companies that may want to use them to find new drugs for the diseases that are included in this bank. While CDI and Coriell are located outside California, they have set up facilities at the Buck Institute in Novato, CA, where they generate and bank the iPS cells for this Initiative.

Which diseases will be represented? The stem cell lines created will represent a variety of diseases or conditions that affect brain, heart, lung, liver or eyes. Grantees come from a variety of California-based institutions:

How many samples are being collected? Below is a table that outlines CIRM's collection goalsfor each condition, along with control samples.

* these control donors will be specifically tested for the absence of lung disease

CIRM's New Stem Cell Bank Up, Running (California Healthline)

iPSC Initiative Brochure [PDF] Stem Cell FAQ How do scientists model disease with iPSC's

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Induced Pluripotent Stem Cell Initiative | California's ...

Somatic stem cells in the human endometrium.

By adminOctober 7, 2016Somatic Stem Cells

The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Miller School of Medicine | University of Miami

By adminOctober 7, 2016Stem Cell Medical Center

Researchers Innovative Study Links Sustained Poverty to Worse Cognitive Function in Midlife

From left, Adina Zeki Al Hazzouri, Ph.D., with Tali Elfassy, M.S.P.H.

Sustained exposure to economic hardship over two decades was strongly associated with worse cognitive function in relatively young individuals, according to a recent study led by Adina Zeki Al Hazzouri, Ph.D., assistant professor of Epidemiology in the Department of Public Health Sciences at the University of Miami Miller School of Medicine.

Zeki Al Hazzouri, Ph.D., was lead author of the article, Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, published recently in the American Journal of Preventive Medicine. Her Miller School co-author was Tali Elfassy, M.S.P.H., a Ph.D. candidate in Epidemiology. The studys co-authors are Stephen Sidney, M.D., M.P.H., of Kaiser Permanente in Oakland, Calif.; David Jacobs, Ph.D., of the University of Minnesota in Minneapolis; Eliseo J. Perez Stable, M.D., of the National Institute of Minority Health and Health Disparities in Bethesda, and Kristine Yaffe, M.D., from the University of California San Francisco.

Stem Cell | Makise Medical Center Japan

By adminOctober 5, 2016Stem Cell Medical Center

Cells develop from only one fertilized egg --- zygote. A "Totipotent Cell" with the ability to differentiate into more than 220 cell types. except placenta. But its Totipotency, (which represents the cell with the greatest differentiation potential) is not retained during all the various stages of cell sub-division.

The first sub-division provides 2 Totipotent cells. The second 4 cells, retain Totipotency But the following 8 cells no longer retain the ability to differentiate into all types of cells. Further sub-divisions differentiate into specialized cells such as fibroblasts, erythrocytes, nerve cells, intestinal mucosal epithelial cells and pancreatic islet cells, etc. but following 6 to 7 full further cell sub-divisions (about 5 days after fertilization), the embryo becomes a "Blastocyst" and possesses "Inner Cell Mass (ICM) "

ICM cells can differentiate into any cell type, except placenta --- pluripotency. 3 weeks after fertilization, the cells of the inner cell mass differentiate into ectoderm, mesoderm and endoderm. In the 1950s, this differentiation was thought to be irreversible, being described as a ball rolling down a hill and technically known as " Epigenetic Landscape".

This was until 1962 when John Gurdon created clone frogs and then in 1996 Ian Wilmut created "Dolly " the cloned sheep. Scientists had previously thought stem cells could not have pluripotency once dispersed into a specialized cell. however, in nature, even once differentiated, some cells can again differentiate and this phenomenon is known to science.

The stem cells of humans have limited ability to differentiate. But for example, Planaria that is a small flatworm living in rivers has amazing ability to differentiate into any organs, even into itself. When it is chopped into 3 fragments like picture, each fragment regenerates to a perfect Planaria. There is a record that 1/279 fragment of one Planaria regenerated to perfect Planarias. When Planaria grows to a certain size, it divides itself to two fragments. And each fragment grows to a perfect Planaria. For Planaria, division and regeneration are mechanism for reproduction. But under some circumstances Planaria chooses sexual reproduction.

A Plant can regenerate itself from one already differentiated cell. An Enzyme mixture of Cellulase Onozuka R-10 and Macerozyme R-10 dissolves tobacco plant (Nicotiana tabacum) leaf cell walls, and cells become leaf protoplasts (= cell without cell walls). When protoplasts are cultivated under appropriate condition, the protoplasts grow to a seedling plant through plant callus (= mass of unorganized parenchyma cells). When the seedling plant is planted in soil, it grows to a perfect tobacco plant.

Two British scientists proved biological technique could change Epigenetic Landscape.

Gurdon created cloned frogs.

Wilmut used a cell nucleus which had been differentiated in the mammary gland.

Human embryos reach "Blastocyst" about 5 days' post fertilization. The Blastocyst possesses an "Inner Cell Mass (ICM) " In 1981 Martin Evans succeeded in culturing mouse ICM cells. These cells are capable of propagating themselves indefinitely in an undifferentiated state, and they can differentiate into any type of cell except placenta. These cells are pluripotent, and known as Embryonic Stem Cell (ES Cells). James Thomson created ES Cells from Monkey embryo in 1995 and later in 1998 created ES Cells from human embryo. However, research into ES Cell needs further study due to an ethical dilemma, that in order to isolate inner cells from the blastocyst, the blastocyst is destroyed, so is the embryo at pre-implantation stage to be considered human? and even if not, do we have the right to destroy human potential growth.

The ethical issue of ES Cells can be by-passed by using Induced pluripotent stem cells. The iPS cell is a pluripotent stem cell which can be generated directly from adult cells, not from human embryos, and in 2006, Shinya Yamanaka and his team in Kyoto University created iPS cells from mouse fibroblasts.

He hypothesized that the genes playing a pivotal role in the function of ES Cells could induce an embryonic state in adult cells. But how many are the genes? The human has 20 - 25 thousand genes. Yamanaka researched and found 24 genes which were important for the characteristic protein of human ES Cells, and then used retroviruses to deliver all 24 genes into mouse fibroblasts, and the fibroblasts were able to propagate indefinitely. These iPS Cells were pluripotent like ES Cells.

Yamanaka removed one factor at a time from the 24 factors to identify the necessary genes for reprogramming and by this process he identified 4 factors -- Oct3/4, Sox2m Klf4 and c-Myc - named the "Yamanaka Factors", and Later he found c-Myc was not needed for reprogramming, but without c-Myc the process took longer and was inefficient.

A strong concern of the iPS researchers was if iPS Cell differentiation caused cancerous cells. But this issue has almost been resolved completely through rigorous study. And many clinical human applications are now carried out in Japan. For example, in 2014 retina transplantation by iPS Cells was successfully carried out for age-related macular degeneration. And cells did not differentiate into cancer cells. In my next page, I write more about these applications.

iPS Cells are useful not just for regenerative medicine but for drug discoveries or development. Because it is very easy for researchers to recreate special cells which cause special diseases, in a petri dish --- Alzheimer's disease, Parkinsons disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia.

For example, "Achondroplasia" which is caused by mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. Researchers made iPS Cells from skin fibroblasts of 3 patients with achondroplasia then allowed the iPS Cells to differentiate into chondrocytes over 2 to 3 weeks. Chondrocytes in the petri dish secreted about themselves an extracellular matrix which is characteristic of chondrocytes and made a mass. Compared to the chondrocytes of healthy people, these patients chondrocytes grew slowly, and the researchers tried thousands of drugs one by one to cure the abnormal chondrocytes from the petri dish specimens. Then finally, and with much surprise, they found the "Statin drug" was effective and able to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are for lowering cholesterol, and nobody expected cholesterol lowering drugs to be effective against achondroplasia.

In the next pages I explain in more detail about practical and clinical uses of iPS Cells.

The researchers of iPS Cells were most afraid of differentiation of iPS Cells into cancer cells. But now this problem has been almost solved by rigorous studies. And many clinical applications for humans are being done in Japan. For example, in 2014 transplantation of iPS Cells of retina was successfully done for age-related macular degeneration in Japan. The cells have not differentiated into cancer cells. In the next page, I write more about the applications.

iPS Cell is very useful not only for regeneration medicine but also for drug discovery or drug development. Because it is very easy for researchers to make the special cells that cause the special diseases --- Alzheimer's disease, Parkinson's disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia -- in petri dish.

For example, Achondroplasia that is caused by a mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. The researchers made iPS Cells from the skin fibroblasts of the 3 patients of achondroplasia and let the iPS Cells differentiate into chondrocytes in 2 to 3 weeks. The chondrocytes in petri dish secreted around themselves an extracellular matrix that is characteristic of chondrocytes and made a mass. The chondrocytes from the patients grow very slow compared with the chondrocytes from those of healthy people. The researchers tried thousands of drugs one by one to cure abnormal chondrocytes from the patients in petri dish. Then finally, and with much surprise, they found "Statin drug" was effective to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are drugs for cholesterol lowering. Nobody expected cholesterol lowering drugs are effective for achondroplasia.

In the next pages, I explain in more detail about practical and clinical use of iPS Cells.

Adult Stem Cells are undifferentiated cells found throughout the body such as in bone marrow, and umbilical cord blood, and the mammary gland, and the surface of the small and large intestines, the adipose tissue, the lining of the nose, the testicles, and the hair follicle, between the basement membrane and the sarcolemma of muscle fibers (Satellite Cells), etc.

These cells are multipotent cells that have less ability to differentiate into specialized cells than pluripotent cells. The adult stem cell from the bone marrow, called Hematopoietic Stem Cell (HSC), was discovered in the 1960s by two Canadian biologists, James Till and Ernest McCulloch, and has been used clinically to cure various blood diseases, such as leukemia, malignant lymphoma, multiple myeloma, etc. Clinically a very important cell. But for regenerative medicine, it needs much practical work to obtain stem cells from bone marrow, and requires general anesthesia, however scientists recently have found it easier to obtain these cells.

This is by ASC (adipose-derived stem cell) from our fat. The first scientific reports on ASC were made by an American scientist, Patricia Zuk (UCLA), in 2001. She reported the presence of mesenchymal stem cells in the fat tissues, and as they have a faster growth rate, these cells are expected to be advantageous for regenerative medicine.

ASC can differentiate into muscle, bone, cartilage, liver, adipose cell (lipid cell). And besides the advantages as stem cell, ASC secrets exsosome (nano size particles) that contain enzymes which dissolve beta-amyloid of Alzheimer's disease. The efficacy is 8 times more potent than the enzymes secreted by the exssome of the bone marrow.

ASC is now aggressively researched in Japan for practical uses. It will be used to treat many diseases such as Alzheimer's, Parkinson's, and diseases of the liver and kidneys, and periodontal disease, and more. For example, please see the video:

In Japan Tottori University Medical School researchers have established the technique of breast reconstruction by ASC after mastectomy due to cancer. They operate and inject ASC into the patients depressed breast. The breast recovers to the original shape within three months. This is not silicon, but the patients own cells. Quite natural. No rejection. The cost of this treatment will be covered by health insurance within three years in Japan. And Doctors at the Nagoya University Medical School use ASC against urinary incontinence stress. The sphincter function of the urethra often weakens due to aging,delivery, and some bladder diseases. ASC is injected around the patients urethra to strengthen the smooth muscle.

However, some side effects may occur by use of ASC. For example, male prostate hyperplasia and female endometriosis. Issues not studied in depth. So for now until the side effects have been dealt with, we should wait for general anti-aging treatments.

Recently it was found possible to induce, directly from somatic cells, not only iPS but nerve cells, hepatocyte cells, myocardium cells, cartilage cells, and many varied cells by introducing the specific key transcription factors in cell differentiation, which means that through by-passing of pluripotent stem cells it is possible to induce differentiated specific cells from somatic cells. This is called "Direct Reprogramming", and the most exciting research for example is: myocardial reprogramming in vivo, where Doctors inject patient's fibroblasts with transcription factors to the infarcted lesion of the heart. There the fibroblasts differentiate into myocardium (heart muscle). So, simple and quick. And this regenerative medical technique is under development mainly in Japan and the United States and as this technique is established, lots of heart surgeries will become obsolete and this is also true of brain surgery. The numbers of hospitals will eventually reduce and cost of time consuming surgeries will lower and this will lead on to a "De-Hospitalized Society".

For a basic understanding of stem cell mechanisms: ES Cell is studied along with iPS Cell and ASC. But ES Cell has an ethical dilemma and this issue shall not be overcome by science. So, it cannot be used for the treatment of human diseases. Direct Reprogramming: Wonderful technology. But it may take 10 or 20 years more to accomplish it. Therefore, at this moment, iPS Cell and ASC are most realistic medical tools for those who are suffering from degenerative diseases and wish rejuvenation.

Go here to see the original:
Stem Cell | Makise Medical Center Japan

Embryonic Stem Cells | Stem Cells Freak

By adminOctober 4, 2016Embryonic Stem Cells

As their name suggests, embryonic stem cells (ESCs) are stem cells that are derived from embryos. If we wanted to be more scientific, we would say that ESCs are pluripotent stem cells derived from a blastocyst, an embryo in a very early stage (4-5 days of age).A blastocyst is consisted of 50-150 cells. ESCs measure approximately 14m in diameter.

The use of human embryonic stem cells is highly controversial, as their extraction requires the destruction of a human embryo, raising a great number of ethical issues. The main one is whether a blastocyst can be considered a living person or not. Check our article, Stem Cell Controversy for more info on this topic

Embryonic Stem cell properties There are two important attributes that distinguish stem cells from any other typical cell:

Embryonic stem cells are pluripotent, having the capacity to differentiate and develop into almost all kinds of cells belonging to thethree primary germ layers:

As for self-renewal, ES cells have the capacity to replicate indefinitely. In other words they have the ability, under the proper conditions, to produce infinite numbers of daughter cells just from one or a few father cells.

Human Embryonic Stem Cell Extraction And Culture First the inner cell mass (ICM) of the blastocyst is separated from the trophectoderm. Then the cells of the ICM are placed on aplastic laboratory culture dish that contains a nutrient broth called the "culture medium". Typically the inner surface of the dish is coated with what is called a "feeder layer", consisting of reprogrammed embryonic mouse skin cells that don't divide. These mouse cells lay in the bottom of the dish and act as a support for the hESCs. The feeder layer not only provides support, but it also releases all the needed nutrients for thehESCs to grow and replicate. Recently, scientists have devised new ways for culturing hESCs without the need of a mouse feeder cell, a really important advance as there is always the danger of viruses being transmitted from the mouse cells to the human embryonic stem cells.

It should be noted that the process described above isn't always successful, and many times the cells fail to replicate and/or survive. If on the other hand, the hESCs do manage to survive and multiply enough so that the dish is "full", they have to be removed and plated into several dishes. This replating and subculturing process can be done again and again for many months. This way we can get millions and millions of hESCs from the handful ones we had at the beginning.

At any stage of the process, a batch of hESCs can be frozen for future use or to be sent somewhere else for further culturing and experimentation.

How are human embryonic stem cells induced to differentiate ? There are various options for researchers to choose from, if they decide to differentiate the cultured cells.

The easiest one, is to simply allow the cells to replicate until the disc is "full". Once the disc is full, they start to clump together forming embryoid bodies(rounded collections of cells ). These embryoid bodies contain all kinds of cells including muscle, nerve, blood and heart cells. As said before, although this is easiest method to induce differentiation, it is the most inefficient and unpredictable as well.

In order to induce differentiation to a specific type of cell, researchers have to change the environment of the dish by employingone of the ways below:

Human Embryonic Stem Cells, potential uses Many researchers believe that studying hESCs is crucial for fully understanding the complex events happening during the fetal development. This knowledge would also include all the complex mechanisms that trigger undifferentiated stem cells to develop into tissues and organs. A deeper understanding of all these mechanisms would in return give scientists a deeper understanding of what sometimes goes wrong and as a result tumours,birth defects and other genetic conditions occur, thus helping them to come up with effective treatments.

Several new studies also address the fact that human embryonicstem cells can be used as models for human genetic disorders that currently have no reliable model system. Two examples are the Fragile-X syndromeandCystic fibrosis.

As of now, there has been only one human clinical trial ,involving embryonic stem cells, with the officialapproval of the U.S. Food and Drug Administration (FDA).The trial started on January 23, 2009, and involved the transplantation ofoligodendrocytes (a cell type of the brain and spinal cord) derived from human embryonic stem cells. During phase I of the trial, 8 to 10paraplegics with fresh spinal cord injuries (two weeks or less) were supposed to participate.

In August 2009,the trial wasput on hold, due to concerns made by the FDA, regarding a small number of microscopic cysts found in several treated rat models. InJuly 30, 2010 the hold was lifted and researchers enrolled the first patient and administered him with the stem cell therapy.

See the article here:
Embryonic Stem Cells | Stem Cells Freak

Japanese scientist wins 2016 Nobel medicine prize | Reuters

By adminOctober 3, 2016Uncategorized

By Niklas Pollard and Kate Kelland | STOCKHOLM/LONDON

STOCKHOLM/LONDON Japan's Yoshinori Ohsumi won the 2016 Nobel prize for medicine for ground-breaking experiments with yeast which exposed a key mechanism in the body's defenses where cells degrade and recycle their components.

Understanding the science behind the process, called "autophagy" or "self-eating", has led to a better understanding of diseases such as cancer, Parkinson's and type 2 diabetes, the prize committee said in its statement on Monday.

"Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content," it said.

The Physiology or Medicine prize, the first of the Nobel prizes awarded each year, is worth 8 million Swedish crowns ($933,000).

Ohsumi, born in 1945 in Fukuoka, Japan, has been a professor at the Tokyo Institute of Technology since 2009. He told Kyodo News agency he was "extremely honored" to get the prize.

In a separate interview with broadcaster NHK, he said he had "always wanted to do something that other people wouldnt do".

"I thought the breakdown (of cells) would be interesting, and that was my start," he said.

Ohsumi's work - carried out in the 1990s and described by commentators as "paradigm-shifting" and "pioneering" - included locating the genes that regulate autophagy. This is important for medicine because it helps show why errors in these genes can contribute to a range of diseases.

David Rubinsztein, deputy director of Cambridge University's Institute for Medical Research, said Ohsumi had provided scientists around the world with "critical tools" to help them understand how disrupted autophagy can contribute to illnesses including infectious diseases, cancers and neurodegenerative diseases such as Huntingtons and Parkinsons.

Chister Hoog, a professor at Sweden's Karolinska Institute, told Reuters the work helped explain crucial processes in human development, from growing up, to aging to succumbing to disease.

"In the very early stages (of a humans development) your organs and your whole body is constantly being made over again you are growing. So you need to get rid of the old stuff and generate new structures," he said.

"When you undergo aging, you have structures that have to be taken away and this autophagy is the principle that gets rid of them.

"If you affect this system the genes and proteins involved in autophagy you no longer can take care of the waste, and once it accumulates you will get some type of disease."

This year, the Karolinska Institute, which awards the Nobel medicine prize, has been immersed in a scandal over the hiring of a controversial surgeon. The Swedish government dismissed several members of the board in September.

Prizes for achievements in science, literature and peace were first awarded in 1901 in accordance with the will of dynamite inventor and businessman Alfred Nobel. ($1 = 8.5776 Swedish crowns)

(This version of the story fixes the typo in the name of the Karolinska professor)

(Additional reporting by Stockholm Newsroom and by Minami Funakoshi in Tokyo; Editing by Alistair Scrutton and Robin Pomeroy)

SAN FRANCISCO California will allow companies more leeway in testing self-driving cars on public roads while restricting how the nascent technology is advertised under revised draft regulations released on Friday.

German luxury auto maker BMW AG said on Friday it will offer all electric versions of its next generation BMW X3 compact sport utility vehicle and electric Mini models, expanding its entries in the emerging electric luxury vehicle market.

BRUSSELS U.S. software company Salesforce called on EU regulators on Thursday to investigate antitrust issues related to Microsoft's $26 billion bid for social network LinkedIn.

Continued here:
Japanese scientist wins 2016 Nobel medicine prize | Reuters

Hematology Conferences | Blood Disorder Conferences | USA …

By adminOctober 3, 2016Uncategorized

6thInternational Conference on Hematology

Date:October 03-05, 2016

Venue:Orlando, Florida, USA

Hematology 2016 has been designed with many interesting and informative scientific sessions; it includes all possible aspects of Hematology research.

Hematology

Erythrocytesare also known as red blood cells which carry oxygen to the body and collect carbon dioxide from the body by the use of hemoglobin and its life span of 120 days. along the side the leucocytes helps in protecting the healthy cells because the W.B.C (leucocytes) act as the defending cells in protecting the immune system from the foreign cells. Theseleucocytesare multipotent cells in bone marrow and there life span is of 3-4 days where the yellow blood cells are called as thrombocytes they are where small and irregular in shape they have life span of 5-9 days they are mostly seen in mammals they help in clotting of blood which are in fibrin form called as thrombosis these lead to heart stroke, blockage of blood in blood mostly in arms and legs. where C.B.C is known ascomplete blood countis done to know the number of cells in a body these are mainly done by lab technician presently they are been tested by automatic analyzer the high and low amount of cells will lead to many diseases. Decrease of R.B.C in the body these causes of anemia which leads to weakness, feeling of tired, shortness of breath and person will be noticeably pale. Formation of blood cellular components are called as Hematopoiesis and all the cellular blood components are derived from hematopoiesis stem cells in a healthy individual nearly 10111012new blood cells are produced these help in steady peripheral circulation. If there is a increases of R.B.C in the body these causes polycythemia these can be measured through hematocrit level.

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International Conference onGenetic CounselingandGenomic MedicineAugust 11-12, 2016, UK; International Conference onClinicalandMolecular GeneticsNovember 28-30, 2016, USA; 5thInternational Conference and Exhibition onCellandGene TherapyMay 19-21, 2016, USA; World Congress onHuman GeneticsOctober 31- November 02, 2016, Spain; International Conference onNext Generation SequencingJuly 21-22, 2016, Germany; 58th ASH Annual Meeting & Exposition December 3-6, 2016 San Diego, CA; ESH 2016 Annual Meeting June 10 13, 2016 Paris, France; ASH Conferences on Lymphoma Biology June 18 - 21, 2016 ESH 5th International Conference on Myelodysplastic Syndromes April 14 April 16, 2016 Estoril, Portugal; European Society ofHuman Genetics: ESHG Conferences May 21-24, 2016, Spain; American Society ofHuman Genetics;ASHG Annual Meeting October 6-10, 2015, Maryland.

Blood Disorders

Hemophilia Ais a genetic deficiency in clottingfactor VIII,which causes increased bleeding and usually affects males. About 70% of the time it is inherited as an X-linked recessive trait, but around 30% of cases arise from spontaneous mutations. Hemophilia B is ablood clottingdisorder caused by amutationof thefactor IXgene, leading to a deficiency of factor IX. It is the second-most common form ofhaemophilia, rarer thanhaemophilia A. It is sometimes calledChristmas disease, named afterStephen Christmas, the first patient described with this disease.In addition, the first report of its identification was published in the Christmas edition of theBritish Medical Journal.Hemophilia C is a mild form of haemophiliaaffecting both sexes. However, it predominantly occurs in Jews ofAshkenazidescent. It is the fourth most common coagulationdisorder aftervon Willebrand's diseaseandhaemophiliaAandB.In theUSAit is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A. Idiopathic thrombocytopenic purpura(ITP), also known asimmune thrombocytopenia,primary immune thrombocytopenia,primary immune thrombocytopenic purpuraorautoimmune thrombocytopenic purpura, is defined as isolated low platelet count (thrombocytopenia) with normalbone marrowand the absence of other causes of thrombocytopeniaVon Willebrand diseasesis the most common hereditarycoagulationabnormality described in humans. Platelets also called "thrombocytes" areblood cellswhose function (along with thecoagulation factors) is to stop bleeding by clumping and clogging blood vessel injuries.Platelets have nocell nucleus: Coagulation is highlyconservedthroughout biology; in allmammals, coagulation involves both a cellular (platelet) and aprotein(coagulation factor) component and these are occoured due togenetic blood disorders

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Hematologic Malignancies

Lymphatic leukemiawhich effect the white blood cells(w.b.c) they are closely related to the lymphomas and some of them are unitary diseases which related to the adult T cells leukemia these come under the lymphoproliferative disorders. Mostly they involve in the B-cell sub type lymphocytes. The myeloid leukemia is preferred to the granulocyte precursor in the bone marrow and spinal cord and these arises the abnormal growth in the blood from tissues in the bone marrow. They are mainly related to the hematopoietic cells and these sub title into acute and chronic lymphoblastic leukemia. The acute leukemia is that rapidly producing immature blood cells as they are bulk number of cells healthy cells are not produced in bone marrow due this spill over the blood stream which spread to other body parts. Where as in chronic leukemia highly bulid of matured cells are formed but still abnormal white cells are formed these can not be treated immediately mostly seen in older people. The cancer which originate from white blood cells are called as lymphoma and this disorder is mainly seen inHodgkin lymphomathese diseases is treated by radiation and chemotherapy, orhematopoietic stem cell transplantation. The cancer which starts with in the cell are called as Non Hodgkin lymphocytes and these lymphocytes are of lymph nodes. The bone marrow which develops too many white blood cells leads tomultiple myleoma. The further details on malignance are been discussed inHematology oncology conference-2015.

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Hematology and immunology

Blood groupsare of ABO type and but at present the Rh blood grouping of 50 well defined antigens in which 5 are more important they are D,C,c,E and e and Rh factors are of Rh positive and Rh negative which refers to the D-antigen. These D-antigen helps in prevention of erythroblast fetalis lacking of Rh antigen it defined as negative and presences of Rh antigen in blood leads to positive these leads to rh incompatibility. The prevention treatment of diseases related to the blood is called as the Hematology. The hematologists conduct works on cancer to. The disorder of immune system leading to hypersensitivity is called asClinical Immunologyand the abnormal growth of an infection are known as Inflammation and the arise of an abnormal immune response to the body or an immune suppression are known as Auto immune disorder. The stem cell therapy is used to treat or prevent a disease or a condition mostly Bone marrow stem cell therapy is seen and recently umbilical cord therapy Stem cell transplantation strategies remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases.

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Blood Transplantation

Theumbilical cordis a conduit between the developingembryoorfetusand theplacenta. The umbilical vein supplies the fetus with nutrient-richbloodfrom theplacenta The hematopoitic bone marrow transplant, the HSC are removed from a large bone of the donor, typically thepelvis, through a largeneedlethat reaches the center of the bone. Acute myeloid leukemia is a cancerof themyeloidline of blood cells, characterized by the rapid growth of abnormalwhite blood cellsthat accumulate in thebone marrowand interfere withthe production of normal blood cells and the Thrombosis is the formation of ablood clot inside ablood vessel, obstructing the flow ofbloodthrough thecirculatory system. TheHemostaticis a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel this is the first stage of wound healing. Metabolic syndromeis a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions, obesity,elevated blood pressure,elevated fasting plasma glucose,high serum triglycerides, and lowhigh-density lipoprotein(HDL) levels. Metabolic syndrome increases the risk developingcardiovascular diseaseanddiabetes.

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Diagnosis and Treatment

Palliative careis amultidisciplinary approachto specialisedmedical carefor people with seriousillnesses The spleen, similar in structure to a largelymph node, acts as a blood filter. Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Some anticoagulants are used in medical equipment, such astest tubes ,blood transfusionbags, andrenal dialysisequipment. Anvena cava filteris a type of vascular filter, amedicaldevice that is implanted byinterventional radiologistsor vascular surgeons into theinferior vena cavato presumably prevent life-threateningpulmonary emboliistherapyusingionizing radiation, generally as part of cancer treatmentto control or killmalignantcells. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. The subspecialty ofoncologythat focuses on radiotherapy is calledradiation oncology. Translational research is another term fortranslated researchandtranslational science, Applying knowledge from basic science is a major stumbling block in science, partially due to the compartmentalization within science. Targeted drug delivery is a method of deliveringmedicationto a patient in a manner that increases theconcentrationof the medication in some parts of the body relative to others.

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New Drug Development in Haematology

The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules. Because the drugisso specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Known asDrug deliveryConditions treated with combination therapy includetuberculosis,leprosy,cancer,malaria, andHIV/AIDS. One major benefit of combination therapies is that they reduce development ofdrug resistance, since a pathogen or tumor is less likely to have resistance to multiple drugs simultaneously.Artemisinin-based monotherapies for malaria are explicitly discouraged to avoid the problem of developing resistance to the newer treatment. Drug Induced Blood Disorders causes of sickle cell anemia,pale skin non steroids antiinflammatory drugswhich causes ulcers Using drug repositioning, pharmaceutical companies have achieved a number successes, for examplePfizer'sViagrainerectile dysfunctionandCelgene'sthalidomidein severe erythema nodosum leprosum. Smaller companies, including Ore Pharmaceuticals,Biovista, Numedicus,Melior Discoveryand SOM Biotech are also performing drug repositioning on a systematic basis. These companies use a combination of approaches including in silico biology and in vivo/in vitro experimentation to assess a compound and develop and confirm hypotheses concerning its usage for new indications.

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Hematology Research

Lymphatic diseasesthis is a type of cancer of the lymphatic system. It can start almost any where in the body. It's believed to be caused by HIV, Epstein-Barr Syndrome, age and family history. Symptoms include weight loss, fever, swollen lymph nodes, night sweats, itchy skin, fatigue, chest pain, coughing and/or trouble swallowing. Thelymphatic systemis part of thecirculatory system, comprising a network oflymphatic vesselsthat carry a clear fluid called lymph directionally towards the heart. The lymphatic system was first described in the seventeenth century independently byOlaus RudbeckandThomas Bartholin. Unlike thecardiovascular systemthe lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres ofbloodper day throughcapillary filtrationwhich removesplasmawhile leaving theblood cells. Roughly 17 litres of the filtered plasma get reabsorbed directly into the blood vessels, while the remaining 3 litres are left behind in theinterstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus 3 litres. Lymphatic diseases are ofNon-Hodgkin's Lymphoma, Hodgkins. Thethymusis a specialized primarylymphoidorgan of theimmune system. Within the thymus,T cellsor Tlymphocytesmature. T cells are critical to theadaptive immune system, where the body adapts specifically to foreign invaders.One of the example of lymph node development. Formation oflymph nodeinto the tumor which lead to cancer called oncology.

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Various Aspects of Haematology

Pediatric Haematology and Oncologyis an internationalpeer-reviewedmedical journalthat covers all aspects ofpediatrichematologyandoncology. The journal covers immunology, pathology, and pharmacology in relation to blood diseases and cancer in children and shows how basic experimental research can contribute to the understanding of clinical problems. Physicians specialized in hematology are known ashematologistsorhaematologists. Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewingblood filmsandbone marrowslides under themicroscope, interpreting various hematological test results andblood clotting testresults. In some institutions, hematologists also manage the hematology laboratory. Physicians who work in hematology laboratories, and most commonly manage them, are pathologists specialized in the diagnosis of hematological diseases, referred to as hematopathologistsorhaematopathologists.Experimental Hematologyis apeer-reviewedmedical journalofhematology, which publishesoriginal researcharticles and reviews, as well as the abstracts of the annual proceedings of theSociety for Hematology and Stem Cells and they should be done under theHematology guidlines.

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Blood Based Products

Ablood substituteis a substance used to mimic and fulfill some functions ofbiologicalblood. It aims to provide an alternative toblood transfusion, which is transferring blood orblood-based productsfrom one person into another. Thus far, there are no well-acceptedoxygen-carryingblood substitutes, which is the typical objective of ared blood celltransfusion; however, there are widely available non-bloodvolume expandersfor cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood.Pathogen reductionusing riboflavin and UV lightis a method by which infectiouspathogensinblood for transfusionare inactivated by addingriboflavinand irradiating withUV light. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as pathogen inactivation in the industry. Anartificial cellorminimal cellis an engineered particle that mimics one or many functions of abiological cell. The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such,nanoparticles,liposomes,polymersomes, microcapsules and a number of other particles have qualified as artificial cells.Manufacturing of semi synthetic products of drugs are known as therapeutic biological products.Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Such substances occur naturally in leeches and blood-sucking insects.

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Summary

Hematology is a branch of biology that includes various research areas such as pathology, internal medicine, clinical laboratory, physiology, immunology and pediatrics. This conference will witness a conglomeration of various arenas in Hematology and as it involves a vast range of medical streams within it, this conference will be an excellent platform for interdisciplinary interactions, to exchange and share knowledge under a single roof.

The organizing committee is gearing up for an exciting and informative conference program including plenary lectures, symposia, workshops on a variety of topics, poster presentations and various programs for participants from all over the world. We invite you to join us at the Hematology 2016, where you will be sure to have a meaningful experience with scholars from around the world.

For more details please visit: http://hematology.conferenceseries.com/

Importance & Scope:

Hematology 2016,Orlando, Florida, USAis expected to offer the best platform for the expertise, researchers, students and business delegates with its well organized scientific program covering every minute detail about hematology and blood diseases, from the basic causes behind blood diseases to the latest trends in diagnostic and treatment of blood diseases. This international event is an effort to find a weapon against chronic disorders like blood cancer, Sickle cell anemia, hemophilia, lymphoma and myeloma and to discuss the role of Immunoglobulin in blood, antibody and antigen reactions, the red blood cell and the immunological properties of blood which gives a better insight about the associated causes and disease portfolio.

Conferenceseries LLC welcomes all the hematologists, immunologists, pathologists, oncologists, research scholars, industrial professionals and student delegates from biomedical and healthcare sectors to be a part of the esteemed Hematology 2016. Advanced Diagnostic and therapeutic equipment along with the novel drugs for the blood diseases are an integral part of the Hematology research, hence it will be an excellent amalgamation of academia and industry as it involves every aspects of empirical and conceptual thinking in exploring new dimensions in this field. It is open to all types of research methodologies both from academia and industry.

Why Orlando?

Orlando is a city in the U.S. state of Florida, and the county seat of Orange County. Located in Central Florida, it is the center of the Orlando metropolitan area, which had a population of 2,134,411 at the 2010 census, making it the 26th largest metropolitan area in the United States, the sixth largest metropolitan area in the Southern United States, and the third largest metropolitan area in the state of Florida. In 2010, Orlando had a city-proper population of 238,300, making it the 77th largest city in the United States, the fifth largest city in Florida, and the states largest inland city.

The City of Orlando is nicknamed The City Beautiful and its symbol is the fountain at Lake Eola. Orlando is also known as The Theme Park Capital of the World and in 2014 its tourist attractions and events drew more than 62 million visitors. The Orlando International Airport (MCO) is the thirteenth busiest airport in the United States and the 29th busiest in the world. Buddy Dyer is Orlandos mayor. Orlandos famous attractions form the backbone of its tourism industry: Walt Disney World Resort, located approximately 21 miles (34 km) southwest of Downtown Orlando in Bay Lake, opened by the Walt Disney Company in 1971; the Universal Orlando Resort, opened in 1999 as a major expansion of Universal Studios Florida; SeaWorld; Gatorland; and Wet n Wild. With the exception of Walt Disney World, most major attractions are located along International Drive. The city is also one of the busiest American cities for conferences and conventions.

Conference Highlights

A Unique Opportunity for Advertisers and Sponsors at this International event

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Associations in USA

Associations Worldwide

Universities in USA

Universities Worldwide

Companies in USA

Hospitals in USA

Hospitals in Worldwide

Glance at Market of Hematology

According to market study, market value of Hematology at present is $15.13 billion. A major part of research is going on at the top Universities across the globe, the grants allotted for this research field is around $10.54 billion. Many companies are associated with the blood testing equipment along with various diagnostic instruments, hematologic drugs and other therapeutics, the revenue generated is around $21.1 billion on average by this companies. Besides this various societies and research labs are also associated in this research field. More than 40% research work on Hematology is going on in USA, as around 176 Universities in USA are working in this field, along with 24 Societies, besides that there are almost 40 companies in USA which deals with diagnostic and testing equipment. Market value of Hematology at present in USA is $3.13 billion at present, university grants allotted by government is about $2.10 billion and average revenue generated by the industries in USA is $8.1billion. The global hematology market is divided into hematology products& hematology services. The hematology products segment holds the largest share of the hematology market in 2016. It is also expected to grow at the highest growth rate by next five years, owing to the increasing development of new hematology reagents. In addition, based on the end-users, the global hematology market has been segmented into commercial organizations, stand-alone hospitals, research institutes, and clinical testing labs. The clinical testing labs hold the largest share of the hematology market in 2016.

"3rd International Conference on Hematology & Blood Disorders" organized by OMICS Group International was successfully held at Double Tree by Hilton Hotel Atlanta Airport at Atlanta, USA during November 02-04, 2015. The conference was organized around the theme Research strategies, advanced technologies and upcoming challenges in Hematology."

The conference was marked with the presence of renowned scientists, talented young researchers, students and business delegates representing more than 25 different countries ultimately driving the event into the path of success.

OMICS Group International would like to convey a warm gratitude to all the honorable guests of Hematology-2015, Robert H Schiestl University of California, USA; C Cameron Yin University of Texas, USA; Dianzheng Zhang, Philadelphia College of Osteopathic Medicine, USA;Jay S Raval, University of North Carolina, USA and Robert Michael Davidson The American Institute of Stress, USA

The highlights of the conference were its educative and effectual keynote lectures by:

Robert H Schiestl, University of California, USA

C Cameron Yin , University of Texas, USA

Knox Van Dyke, West Virginia University, USA

Knox Van Dyke,West Virginia University, USA

Robert Michael Davidson , The American Institute of Stress, USA

OMICS Group also took the privilege of felicitating Hematology-2015 Organizing Committee, Editorial Board Members and Keynote Speakers whose support led the conference into the path of excellence. Our special gratitude to our media partnersAll Congress,Business Vibes,Clocate, Medical News Today,Oncology Education and ORIC Publications.

Hematology-2014

"2ndInternational Conference on Hematology & Blood Disorders" organized by OMICS Group International was successfully held at Double Tree by Hilton Hotel BWI Airport at Baltimore, USA during September 29- October 01, 2014. The conference was organized around the themeOn the Path of Identifying Novel Therapeutics for Blood Disorders."

OMICS Group International would like to convey a warm gratitude to all the honorable guests of Hematology-2014, Mark Roschewski, National Institutes of Health, USA; E. Brad Thompson, University of Houston, USA; Britt Gustafsson, Center for Allogeneic Stem Cell Transplantation, Sweden; Effie Liakopoulou, Genimbi Inc, USA and Ping Xie, Rutgers University, USA

The highlights of the conference were its educative and effectual keynote lectures by:

OMICS Group also took the privilege of felicitating Hematology-2014 Organizing Committee, Editorial Board Members and Keynote Speakers whose support led the conference into the path of excellence. Our special gratitude to our exhibitorOne Lambda, USA and media partnersAll Congress,Business Vibes,Clocate, Medical News Today,Oncology Education and ORIC Publications.

Hematology-2013

The highlights of the conference were its educative and effectual keynote lectures by:

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Hematology Conferences | Blood Disorder Conferences | USA ...

Induced Pluripotent Stem Cells: 10 Years After the …

By adminSeptember 28, 2016Induced Pluripotent Stem Cells

Human cortex grown in a petri dish. Eye diseases treated with retinal cells derived from a patients own skin cells. New drugs tested on human cells instead of animal models.

Research and emerging treatments with stem cells today can be traced to a startling discovery 10 years ago when Shinya Yamanaka, M.D., Ph.D., and his graduate student Kazutoshi Takahashi, Ph.D., reported a way to reprogram adult mouse cells and coax them back to their embryonic state pluripotent stem cells.

A year later, they accomplished the feat with human cells. For this research coup and his leading role pioneering stem cell work, Yamanaka who holds academic appointments at Kyoto University and UC San Francisco was the co-recipient of the 2012 Nobel Prize in Medicine or Physiology.

The breakthrough provides a limitless supply of induced pluripotent stem cells (iPSCs) that can then be directed down any developmental path to generate specific types of adult cells, from skin to heart to neuron, for use in basic research, drug discovery and treating disease.

The achievement opened up a practical way and in some critical cases, the only way to directly study human diseases in a dish, and track the early stages of both healthy and abnormal development. It also allowed researchers to screen new drugs directly in human cells rather than relying on animal models, which more often than not fail to accurately predict a new drugs effects on people.

The dazzling iPSC breakthrough has spurred rapid progress in some areas and posed major challenges in others. It has already proved a boon to basic research, but applying the new technology to treat diseases remains daunting. Some types of cells have proved difficult to reprogram, and even the protocols for doing so are still in flux as this is still a very young field.

For many basic biomedical scientists, the capability offered by iPSCs technology is like a dream come true, says neuroscientist Arnold Kriegstein, M.D., Ph.D., director of UCSFs Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.

Induced pluripotent stem cells have given us a window into human development unlike anything we had before, Kriegstein said. Im interested in the early development of the brains cortex. Of course, weve never had unrestricted access to living human brain cells. Now we can take skin cells and grow human cortex in a dish. Its a game-changer for discovery about early human development.

Kriegstein is enthusiastic about what researchers can learn from organoids a pea-sized stage of a developing organ derived from iPSCs. By this stage, cells are already clumping together and starting to signal and differentiate into what will become the adult organ.

Its a very close model of the real thing, Kriegstein says. We have recently discovered that even in this early stage, the organoids are able to develop intrinsic organization, including a front-and-back orientation, and different parts start to look like they do in the embryonic brain.

Some scientific papers have suggested that organoids can model diseases found in adulthood even disorders of late adulthood such as Alzheimers disease.

Even though organoids can reveal developmental steps not seen before, Kriegstein worries that some researchers are getting too far ahead of themselves.

Its an embryonic brain, he stresses. The longest period of growth we can model would be full fetal development. How likely is it that gene expression, cell signaling and a myriad of other interactions at this organoid stage could accurately represent the development of Alzheimers disease, a disease that affects people at 60 or 70?

I think we need to take some of these studies with a grain of salt. Stem cell technology now is so variable that replication is difficult. We need to establish protocols to reliably compare different methods and then use these standardized methodologies to advance research and treatment. But I am 100 percent convinced that we will get there.

Yamanaka currently directs the 500-person Center for iPS Cell Research and Application at Kyoto University, runs a research lab at the Gladstone Institute for Cardiovascular Disease in San Francisco, and serves as a professor of anatomy at UCSF, and Takahashi is a visiting scientist at the Gladstone Institutes and runs Yamanakas lab there. Both have continued to build on their iPSC work, as have other researchers.

In their seminal work, Yamanaka and Takahashi had introduced four genetic factors to prompt adult cells back to the pluripotent state. Soon after their iPSC breakthrough, Sheng Ding, Ph.D., who has a lab at the Gladstone Institutes and is a professor in UCSF's Department of Pharmaceutical Chemistry, began refining the reprogramming cocktail.

Eventually, Ding was able to substitute drug-like molecules for these gene transcription factors, eliminating the risk of new genetic material altering the cells. Today, labs around the world pursue and tout different chemical recipes, often depending on the type of cell they are trying to reprogram.

Other recent advances to induce pluripotency harness different kinds of proteins that influence gene activity in the cell nucleus. Robert Blelloch, M.D., Ph.D., a stem cell scientist at UCSFs Broad Center, has shown that some small RNA molecules called microRNAs promote adult cell de-differentiation and others promote the reverse: ability of stem cells to differentiate into adult cells. By tweaking microRNA activity, his lab has been able to improve reprogramming yields a hundred-fold.

He and colleagues have also become intrigued by the role of so-called epigenetic factors naturally occurring or introduced molecules that modify proteins in the nucleus. Manipulation of these molecules too can affect the efficiency of inducing pluripotent cells.

Six years after Yamanakas iPSCs discovery, researchers in a very different field developed a new gene-editing technology of unprecedented speed and precision, known as CRISPR-Cas9. The potent new tool has revolutionized efforts to cut and paste genes and has been very quickly adopted by thousands of researchers in basic biology and drug development.

CRISPR has provided us with an extraordinary new capability, Kriegstein says. It allows us to tease apart the genetic causes or contributors to developmental diseases. We can edit out mutations to determine if they are critical to early developmental defects.

CRISPRs speed and precision may some day allow stem cell researchers to reach their most ambitious goal: Genetically abnormal cells from patients with inherited diseases such as sickle cell anemia or Huntingtons could be reprogrammed to the pluripotent stem cell state; their genetic defects could be edited in a petri dish before being differentiated into healthy adult cells. These cells could then be transplanted into patients to restore normal function.

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Stem Cell Basics V. | stemcells.nih.gov

By adminSeptember 27, 2016Adult Stem Cells

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. One major difference between adult and embryonic stem cells is their different abilities in the number and type of differentiated cell types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin.

Embryonic stem cells can be grown relatively easily in culture. Adult stem cells are rare in mature tissues, so isolating these cells from an adult tissue is challenging, and methods to expand their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.

Scientists believe that tissues derived from embryonic and adult stem cells may differ in the likelihood of being rejected after transplantation. We don't yet know for certainwhether tissues derived from embryonic stem cells would cause transplant rejection, since relatively few clinical trialshave testedthe safety of transplanted cells derived from hESCS.

Adult stem cells, and tissues derived from them, are currently believed less likely to initiate rejection after transplantation. This is because a patient's own cells could be expanded in culture, coaxed into assuming a specific cell type (differentiation), and then reintroduced into the patient. The use of adult stem cells and tissues derived from the patient's own adult stem cells would mean that the cells are less likely to be rejected by the immune system. This represents a significant advantage, as immune rejection can be circumvented only by continuous administration of immunosuppressive drugs, and the drugs themselves may cause deleterious side effects.

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