STEMCELL Technologies Inc. Enters a Licensing Agreement …

VANCOUVER, British Columbia--(BUSINESS WIRE)--STEMCELL Technologies Inc. has signed a patent license agreement with iPS Academia Japan, Inc. to license and commercialize iPS Academia Japan, Inc.s patented technologies for induced pluripotent stem cell (iPS cell) research.

This agreement will enable STEMCELL Technologies to develop, manufacture, and distribute products that are optimized for cellular reprogramming. This further expands STEMCELLs extensive portfolio of products for hPSC research, which includes ReproTeSR and TeSR-E7 media for reprogramming, the TeSR family of maintenance media, and the STEMdiff product line for robust and reliable differentiation to various cell lineages.

The patents related to iPS cell technologies licensed by iPS Academia Japan are the result of the groundbreaking research of Professor Shinya Yamanaka of the Center for iPS Cell Research and Application (CiRA) at Kyoto University, Japan. iPS cells hold immense potential for drug development and disease modeling. Somatic cells can be reprogrammed using iPS cell technology and subsequently differentiated into specific cell types of diverse lineages. This enables researchers to develop cell lines for, among other applications, screening potential treatments at the patient level. The personalized nature of this approach ensures greater predictive accuracy in disease modeling and treatment outcome.

About STEMCELL Technologies Inc. As Scientists Helping Scientists, STEMCELL Technologies is committed to providing high-quality cell culture media, cell isolation products and accessory reagents for life science research. Driven by science and a passion for quality, STEMCELL Technologies provides over 2000 products to more than 70 countries worldwide. Our specialty cell culture reagents, instruments and tools are designed to support science along the basic to translational research continuum. To learn more, visit http://www.stemcell.com.

About iPS Academia Japan, Inc. iPS Academia Japan, Inc. (AJ) is an affiliate of Kyoto University, and its main role is to manage and utilize the patents and other intellectual properties held/controlled by Kyoto University and other institutions in the field of iPS cell technologies so that the research results contribute to health and welfare worldwide. AJ was established in Kyoto in June 2008. AJ's patent portfolio consists of approximately 110 patent families (350 patent application cases) in iPS cell technologies as of July 2015, and approximately 150 license arrangements have been executed with domestic or international entities.For more information, visit http://www.ips-cell.net.

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Glossary [Stem Cell Information]

Adult stem cellSee somatic stem cell.

AstrocyteA type of supporting (glial) cell found in the nervous system.

BlastocoelThe fluid-filled cavity inside the blastocyst, an early, preimplantation stage of the developing embryo.

BlastocystApreimplantationembryo consisting of a sphere made up of an outer layer of cells (thetrophoblast), a fluid-filled cavity (theblastocoel), and a cluster of cells on the interior (theinner cell mass).

Bone marrow stromal cellsA population of cells found in bone marrow that are different from blood cells.

Bone marrow stromal stem cells (skeletal stem cells)A multipotent subset of bone marrow stromal cells able to form bone, cartilage, stromal cells that support blood formation, fat, and fibrous tissue.

Cell-based therapiesTreatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cells or tissues.

Cell cultureGrowth of cells in vitro in an artificial medium for research or medical treatment.

Cell divisionMethod by which a single cell divides to create two cells. There are two main types of cell division depending on what happens to the chromosomes: mitosis and meiosis.

ChromosomeA structure consisting of DNA and regulatory proteins found in the nucleus of the cell. The DNA in the nucleus is usually divided up among several chromosomes.The number of chromosomes in the nucleus varies depending on the species of the organism. Humans have 46 chromosomes.

Clone (v) To generate identical copies of a region of a DNA molecule or to generate genetically identical copies of a cell, or organism; (n) The identical molecule, cell, or organism that results from the cloning process.

CloningSee Clone.

Cord blood stem cellsSee Umbilical cord blood stem cells.

Culture mediumThe liquid that covers cells in a culture dish and contains nutrients to nourish and support the cells. Culture medium may also include growth factors added to produce desired changes in the cells.

DifferentiationThe process whereby an unspecialized embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell. Differentiation is controlled by the interaction of a cell's genes with the physical and chemical conditions outside the cell, usually through signaling pathways involving proteins embedded in the cell surface.

Directed differentiationThe manipulation of stem cell culture conditions to induce differentiation into a particular cell type.

DNADeoxyribonucleic acid. DNA is the chemical name for the molecule that carries genetic instructions in all living things.

EctodermThe outermost germ layer of cells derived from the inner cell mass of the blastocyst; gives rise to the nervous system, sensory organs, skin, and related structures.

EmbryoIn humans, the developing organism from the time of fertilization until the end of the eighth week of gestation, when it is called a fetus.

Embryoid bodiesRounded collections of cells that arise when embryonic stem cells are cultured in suspension. Embryoid bodies contain cell types derived from all threegerm layers.

Embryonic germ cellsPluripotent stem cells that are derived from early germ cells (those that would become sperm and eggs). Embryonic germ cells (EG cells) are thought to have properties similar to embryonic stem cells.

Embryonic stem cellsPrimitive (undifferentiated) cells that are derived from preimplantation-stageembryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

Embryonic stem cell lineEmbryonic stem cells, which have been cultured under in vitro conditions that allow proliferation without differentiation for months to years.

EndodermThe innermost layer of the cells derived from the inner cell mass of the blastocyst; it gives rise to lungs, other respiratory structures, and digestive organs, or generally "the gut."

EnucleatedHaving had its nucleus removed.

EpigeneticHaving to do with the process by which regulatory proteins can turn genes on or off in a way that can be passed on during cell division.

Feeder layerCells used in co-culture to maintain pluripotent stem cells. For human embryonic stem cell culture, typical feeder layers include mouse embryonic fibroblasts (MEFs) or human embryonic fibroblasts that have been treated to prevent them from dividing.

FertilizationThe joining of the male gamete (sperm) and the female gamete (egg).

FetusIn humans, the developing human from approximately eight weeks after conception until the time of its birth.

GameteAn egg (in the female) or sperm (in the male) cell. See also Somatic cell.

GastrulationThe process in which cells proliferate and migrate within the embryo to transform the inner cell mass of the blastocyst stage into an embryo containing all three primary germ layers.

GeneA functional unit of heredity that is a segment of DNA found on chromosomes in the nucleus of a cell. Genes direct the formation of an enzyme or other protein.

Germ layersAfter the blastocyst stage of embryonic development, the inner cell mass of the blastocyst goes through gastrulation, a period when the inner cell mass becomes organized into three distinct cell layers, called germ layers. The three layers are the ectoderm, the mesoderm, and the endoderm.

Hematopoietic stem cellA stem cell that gives rise to all red and white blood cells and platelets.

Human embryonic stem cell (hESC)A type of pluripotent stem cells derived from early stage human embryos, up to and including the blastocyststage, thatare capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

Induced pluripotent stem cell (iPSC)A type of pluripotent stem cell, similar to an embryonic stem cell, formed by the introduction of certain embryonic genes into a somatic cell.

In vitroLatin for "in glass;" in a laboratory dish or test tube; an artificial environment.

In vitro fertilizationA technique that unites the egg and sperm in a laboratory instead of inside the female body.

Inner cell mass (ICM)The cluster of cells inside the blastocyst. These cells give rise to the embryo and ultimately the fetus. The ICM may be used to generate embryonic stem cells.

Long-term self-renewalThe ability of stem cells to replicate themselves by dividing into the same non-specialized cell type over long periods (many months to years) depending on the specific type of stem cell.

Mesenchymal stem cellsA term that is currently used to define non-blood adult stem cells from a variety of tissues, although it is not clear that mesenchymal stem cells from different tissues are the same.

MeiosisA specialized cell division in which a single diploid cell undergoes two nuclear divisions following a single round of DNA replication in order to produce four daughter cells that contain half the number of chromosomes as the diploid cell. Meiosis occurs during the formation of gametes, to ensure that fertilization produces an embryo carrying the normal number of chromosomes.

MesodermMiddle layer of a group of cells derived from the inner cell mass of the blastocyst; it gives rise to bone, muscle, connective tissue, kidneys, and related structures.

MicroenvironmentThe molecules and compounds such as nutrients and growth factors in the fluid surrounding a cell in an organism or in the laboratory, which play an important role in determining the characteristics of the cell.

MitosisThe type of cell division that allows a population of cells to increase its numbers or to maintain its numbers. The number of chromosomes remains the same in this type of cell division.

MultipotentHaving the ability to develop into more than one cell type of the body. See also pluripotent and totipotent.

Neural stem cellA stem cell found in adult neural tissue that can give rise to neurons and glial (supporting) cells. Examples of glial cells include astrocytes and oligodendrocytes.

NeuronsNerve cells, the principal functional units of the nervous system. A neuron consists of a cell body and its processesan axon and one or more dendrites. Neurons transmit information to other neurons or cells by releasing neurotransmitters at synapses.

OligodendrocyteA supporting cell that provides insulation to nerve cells by forming a myelin sheath (a fatty layer) around axons.

ParthenogenesisThe artificial activation of an egg in the absence of a sperm; the egg begins to divide as if it has been fertilized.

PassageIn cell culture, the process in which cells are disassociated, washed, and seeded into new culture vessels after a round of cell growth and proliferation. The number of passages a line of cultured cells has gone through is an indication of its age and expected stability.

PluripotentThe state of a single cell that is capable of differentiating into all tissues of an organism, but not alone capable of sustaining full organismal development.

Scientists demonstrate pluripotency by providing evidence of stable developmental potential, even after prolonged culture, to form derivatives of all three embryonic germ layers from the progeny of a single cell and to generate a teratoma after injection into an immunosuppressed mouse.

Polar bodyA polar body is a structure produced when an early egg cell, or oogonium, undergoes meiosis. In the first meiosis, the oogonium divides its chromosomes evenly between the two cells but divides its cytoplasm unequally. One cell retains most of the cytoplasm, while the other gets almost none, leaving it very small. This smaller cell is called the first polar body. The first polar body usually degenerates. The ovum, or larger cell, then divides again, producing a second polar body with half the amount of chromosomes but almost no cytoplasm. The second polar body splits off and remains adjacent to the large cell, or oocyte, until it (the second polar body) degenerates. Only one large functional oocyte, or egg, is produced at the end of meiosis.

PreimplantationWith regard to an embryo, preimplantation means that the embryo has not yet implanted in the wall of the uterus. Human embryonic stem cells are derived from preimplantation-stage embryos fertilized outside a woman's body (in vitro).

ProliferationExpansion of the number of cells by the continuous division of single cells into two identical daughter cells.

Regenerative medicineA field of medicine devoted to treatments in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cell populations or tissues. (See also cell-based therapies).

Reproductive cloningThe process of using somatic cell nuclear transfer (SCNT) to produce a normal, full grown organism (e.g., animal) genetically identical to the organism (animal) that donated the somatic cell nucleus. In mammals, this would require implanting the resulting embryo in a uterus where it would undergo normal development to become a live independent being. The firstmammal to be created by reproductive cloning was Dolly the sheep, born at the Roslin Institute in Scotland in 1996. See also Somatic cell nuclear transfer (SCNT).

SignalsInternal and external factors that control changes in cell structure and function. They can be chemical or physical in nature.

Somatic cellAny body cell other than gametes (egg or sperm); sometimes referred to as "adult" cells. See also Gamete.

Somatic cell nuclear transfer (SCNT)A technique that combines an enucleated egg and the nucleus of a somatic cell to make an embryo. SCNT can be used for therapeutic or reproductive purposes, but the initial stage that combines an enucleated egg and a somatic cell nucleus is the same. See also therapeutic cloning and reproductive cloning.

Somatic (adult) stem cellA relatively rare undifferentiated cell found in many organs and differentiated tissues with a limited capacity for both self renewal (in the laboratory) and differentiation. Such cells vary in their differentiation capacity, but it is usually limited to cell types in the organ of origin. This is an active area of investigation.

Stem cellsCells with the ability to divide for indefinite periods in culture and to give rise to specialized cells.

Stromal cellsConnective tissue cells found in virtually every organ. In bone marrow, stromal cells support blood formation.

SubculturingTransferring cultured cells, with or without dilution, from one culture vessel to another.

Surface markersProteins on the outside surface of a cell that are unique to certain cell types and that can be visualized using antibodies or other detection methods.

TeratomaA multi-layered benign tumor that grows from pluripotent cells injected into mice with a dysfunctional immune system. Scientists test whether they have established a human embryonic stem cell (hESC) line by injecting putative stem cells into such mice and verifying that the resulting teratomas contain cells derived from all three embryonic germ layers.

Therapeutic cloningThe process of using somatic cell nuclear transfer (SCNT) to produce cells that exactly match a patient. By combining a patient's somatic cell nucleus and an enucleated egg, a scientist may harvest embryonic stem cells from the resulting embryo that can be used to generate tissues that match a patient's body. This means the tissues created are unlikely to be rejected by the patient's immune system. See also Somatic cell nuclear transfer (SCNT).

TotipotentThe state of a cell that is capable of giving rise to all types of differentiated cells found in an organism, as well as the supporting extra-embryonic structures of the placenta. A single totipotent cell could, by division in utero, reproduce the whole organism. (See also Pluripotent and Multipotent).

TransdifferentiationThe process by which stem cells from one tissue differentiate into cells of another tissue.

TrophoblastThe outer cell layer of the blastocyst. It is responsible for implantation and develops into the extraembryonic tissues, including the placenta, and controls the exchange of oxygen and metabolites between mother and embryo.

Umbilical cord blood stem cellsStem cells collected from the umbilical cord at birth that can produce all of the blood cells in the body (hematopoietic). Cord blood is currently used to treat patients who have undergone chemotherapy to destroy their bone marrow due to cancer or other blood-related disorders.

UndifferentiatedA cell that has not yet developed into a specialized cell type.

Excerpt from:
Glossary [Stem Cell Information]

Induced pluripotent stem cell therapy – Wikipedia, the …

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle cell anemia.Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells also die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels.[5]

Researchers examined the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing.[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice.[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

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Induced pluripotent stem cell therapy - Wikipedia, the ...

Cell potency – Wikipedia, the free encyclopedia

Cell potency is a cell's ability to differentiate into other cell types.[1][2] The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell which like a continuum begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency and finally unipotency. Potency is taken from the Latin term "potens" which means "having power."

Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and Zygotes are examples of totipotent cells.[3] In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential. Toti comes from the Latin totus which means "entirely."

It is possible for a fully differentiated cell to return to a state of totipotency.[4] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[5]

The human development model is one which can be used to describe how totipotent cells arise.[6] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[7] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[8] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.[9]

In September 2013, a team from the Spanish national Cancer Research Centre were able for the first time to make adult cells from mice retreat to the characteristics of embryonic stem cells thereby achieving totipotency.[10]

In cell biology, pluripotency (from the Latin plurimus, meaning very many, and potens, meaning having power)[11] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[12] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embyronic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[13] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[14] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[15] this technique called reprogramming earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[16] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[17] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[18]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[18]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[13] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[19] hindering their use as ESCs replacements.

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Cell potency - Wikipedia, the free encyclopedia

Stem Cell Key Terms | California’s Stem Cell Agency

En Espaol

The term stem cell by itself can be misleading. In fact, there are many different types of stem cells, each with very different potential to treat disease.

Stem Cell Pluripotent Embryonic Stem Cell Adult Stem Cell iPS Cell Cancer Stem Cell

By definition, all stem cells:

Pluripotent means many "potentials". In other words, these cells have the potential of taking on many fates in the body, including all of the more than 200 different cell types. Embryonic stem cells are pluripotent, as are induced pluripotent stem (iPS) cells that are reprogrammed from adult tissues. When scientists talk about pluripotent stem cells they mostly mean either embryonic or iPS cells

Embryonic stem cells come from pluripotent cells, which exist only at the earliest stages of embryonic development. In humans, these cells no longer exist after about five days of development.

When isolated from the embryo and grown in a lab dish, pluripotent cells can continue dividing indefinitely. These cells are known as embryonic stem cells.

James Thomson, a professor of Anatomy at the University of Wisconsin, isolated the first human embryonic stem cells in 1998. He now shares a joint appointment at the University of California, Santa Barbara, a CIRM-funded institution.

Adult stem cells.are found in the various tissues and organs of the human body. They are thought to exist in most organs where they are the source of new cells throughout the life of the organism, replacing cells lost to natural turnover or to damage or disease.

Adult stem cells are committed to becoming a cell from their tissue of origin, and cant form other cell types. They are therefore also called tissue-specific stem cells. They have the broad ability to become many of the cell types present in the organ they reside in. For example:

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Stem Cell Key Terms | California's Stem Cell Agency

Generating Mice from Induced Pluripotent Stem Cells | Protocol

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JoVE Biology

Michael J. Boland1, Jennifer L. Hazen1, Kristopher L. Nazor1, Alberto R. Rodriguez2, Greg Martin2, Sergey Kupriyanov2, Kristin K. Baldwin1

1Dorris Neuroscience Center & Department of Cell Biology, The Scripps Research Institute, 2Mouse Genetics Core Facility, The Scripps Research Institute

Generating induced pluripotent stem cell (iPSC) lines produces lines of differing developmental potential even when they pass standard tests for pluripotency. Here we describe a protocol to produce mice derived entirely from iPSCs, which defines the iPSC lines as possessing full pluripotency1.

Date Published: 11/29/2012, Issue 69; doi: 10.3791/4003

Keywords: Stem Cell Biology, Issue 69, Molecular Biology, Developmental Biology, Medicine, Cellular Biology, Induced pluripotent stem cells, iPSC, stem cells, reprogramming, developmental potential, tetraploid embryo complementation, mouse

Boland, M. J., Hazen, J. L., Nazor, K. L., Rodriguez, A. R., Martin, G., Kupriyanov, S., et al. Generation of Mice Derived from Induced Pluripotent Stem Cells. J. Vis. Exp. (69), e4003, doi:10.3791/4003 (2012).

The production of induced pluripotent stem cells (iPSCs) from somatic cells provides a means to create valuable tools for basic research and may also produce a source of patient-matched cells for regenerative therapies. iPSCs may be generated using multiple protocols and derived from multiple cell sources. Once generated, iPSCs are tested using a variety of assays including immunostaining for pluripotency markers, generation of three germ layers in embryoid bodies and teratomas, comparisons of gene expression with embryonic stem cells (ESCs) and production of chimeric mice with or without germline contribution2. Importantly, iPSC lines that pass these tests still vary in their capacity to produce different differentiated cell types2. This has made it difficult to establish which iPSC derivation protocols, donor cell sources or selection methods are most useful for different applications.

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Generating Mice from Induced Pluripotent Stem Cells | Protocol

induced pluripotent stem cells – RCN Corporation

Stem cells are cells that divide by mitosis to form either

How the choice is made is still unknown. However, several genes have been found whose activity prevents a daughter cell from differentiating.

The only totipotent cells are the fertilized egg and the first 4 or so cells produced by its cleavage (as shown by the ability of mammals to produce identical twins, triplets, etc.).

In mammals, the expression totipotent stem cells is a misnomer totipotent cells cannot make more of themselves.

Three types of pluripotent stem cells occur naturally:

All three of these types of pluripotent stem cells

In mice and rats, embryonic stem cells can also:

Using genetic manipulation in the laboratory, pluripotent stem cells can now be generated from differentiated cells. These induced pluripotent stem cells (iPSCs) are described below.

Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver, lungs) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that when one accumulates sufficient mutations produce a clone of cancer cells.

Examples:

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induced pluripotent stem cells - RCN Corporation

iPS cells and reprogramming: turn any cell of the body …

The discovery of iPS cells

In 2006, Shinya Yamanaka made a groundbreaking discovery that would win him the Nobel Prize in Physiology or Medicine just six years later: he found a new way to reprogramme adult, specialized cells to turn them into stem cells. These laboratory-grown stem cells are pluripotent they can make any type of cell in the body - and are called induced pluripotent stem cells, or iPS cells. Only embryonic stem cells are naturally pluripotent. Yamanakas discovery means that theoretically any dividing cell of the body can now be turned into a pluripotent stem cell.

So how are these iPS cells made? Yamanaka added four genes to skin cells from a mouse. This started a process inside the cells called reprogramming and, within 2 3 weeks, the skin cells were converted into induced pluripotent stem cells. Scientists can now also do this with human cells, by adding even fewer than four genes.

This short clip introduces the science behind reprogramming. View the full 16-minute film to see the whole story of Shinya Yamanaka's discovery.

IPS cells and embryonic stem cells are very similar. They are self-renewing, meaning they can divide and produce copies of themselves indefinitely. Both types of stem cell can be used to derive nearly any kind of specialized cell under precisely controlled conditions in the laboratory. Both iPS cells and embryonic stem cells can help us understand how specialized cells develop from pluripotent cells. In the future, they might also provide an unlimited supply of replacement cells and tissues for many patients with currently untreatable diseases.

In contrast to embryonic stem cells, making iPS cells doesnt depend on the use of cells from an early embryo. Are there any other differences? Current research indicates that some genes in iPS cells behave in a different way to those in embryonic stem cells. This is caused by incomplete reprogramming of the cells and/or genetic changes acquired by the iPS cells as they grow and multiply. Scientists are studying this in more detail to find out how such differences may affect the use of iPS cells in basic research and clinical applications. More research is also needed to understand just how reprogramming works inside the cell. So at the moment, most scientists believe we cant replace ES cells with iPS cells in basic research.

An important step in developing a therapy for a given disease is understanding exactly how the disease works: what exactly goes wrong in the body? To do this, researchers need to study the cells or tissues affected by the disease, but this is not always as simple as it sounds. For example, its almost impossible to obtain genuine brain cells from patients with Parkinsons disease, especially in the early stages of the disease before the patient is aware of any symptoms. Reprogramming means scientists can now get access to large numbers of the particular type of neurons (brain cells) that are affected by Parkinsons disease. Researchers first make iPS cells from, for example, skin biopsies from Parkinsons patients. They then use these iPS cells to produce neurons in the laboratory. The neurons have the same genetic background (the same basic genetic make-up) as the patients own cells. Thus scientist can directly work with neurons affected by Parkinsons disease in a dish. They can use these cells to learn more about what goes wrong inside the cells and why. Cellular disease models like these can also be used to search for and test new drugs to treat or protect patients against the disease.

Reprogramming holds great potential for new medical applications, such as cell replacement therapies. Since iPS cells can be made from a patients own skin, they could be used to grow specialized cells that exactly match the patient and would not be rejected by the immune system.If the patient has a genetic disease, the genetic problem could be corrected in their iPS cells in the laboratory, and these repaired iPS cells used to produce a patient-specific batch of healthy specialized cells for transplantation. But this benefit remains theoretical for now.

Until recently, making iPS cells involved permanent genetic changes inside the cell, which can cause tumours to form. Scientists have now developed methods for making iPS cells without this genetic modification. These new techniques are an important step towards making iPS-derived specialized cells that would be safe for use in patients. Further research is now needed to understand fully how reprogramming works and how iPS cells can be controlled and produced consistently enough to meet the high quality and safety requirements for use in the clinic.

February 2013 Nature news article on planned clinical trial using iPS cells Stem cells the future: an introduction to iPS cells Research into reprogrammed stem cells: an interactive timeline Stem cell school - multimedia learning module on cellular reprogramming Alzheimer Research Forum 4-part article on iPS cells and disease (September 2010) Nature news feature on challenges in the iPS field (May 2011)

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Induced Pluripotent Stem Cells (iPS) | UCLA Broad Stem …

iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. For example, iPSC can be prodded into becoming beta islet cells to treat diabetes, blood cells to create new blood free of cancer cells for a leukemia patient, or neurons to treat neurological disorders.

In late 2007, a BSCRC team of faculty, Drs. Kathrin Plath, William Lowry, Amander Clark, and April Pyle were among the first in the world to create human iPSC. At that time, science had long understood that tissue specific cells, such as skin cells or blood cells, could only create other like cells. With this groundbreaking discovery, iPSC research has quickly become the foundation for a new regenerative medicine.

Using iPSC technology our faculty have reprogrammed skin cells into active motor neurons, egg and sperm precursors, liver cells, bone precursors, and blood cells. In addition, patients with untreatable diseases such as, ALS, Rett Syndrome, Lesch-Nyhan Disease, and Duchenne's Muscular Dystrophy donate skin cells to BSCRC scientists for iPSC reprogramming research. The generous participation of patients and their families in this research enables BSCRC scientists to study these diseases in the laboratory in the hope of developing new treatment technologies.

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Induced Pluripotent Stem Cells (iPS) | UCLA Broad Stem ...

Pluripotency of Induced Pluripotent Stem Cells

Volume 11, Issue 5, October 2013, Pages 299303

Special Issue: Induced Pluripotent Stem Cells

Edited By Qi Zhou

Induced pluripotent stem (iPS) cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenicity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.

Induced pluripotent stem (iPS) cells can be derived from mouse somatic cells via the ectopic expression of four defined factors, Oct4, Sox2, Klf4 and c-Myc (also known as Yamanaka factors) [1]. The mouse iPS cells express pluripotency markers and both X chromosomes are reactivated, allowing differentiation into various cell types of three germ layers when injected into a blastocyst. iPS technology makes reprogramming much easier [2]and[3] in comparison to early reprogramming methods such as somatic cell nuclear transfer (SCNT) [4]and[5], iPS technology also circumvents the ethical problems arising from the use of human oocytes. In addition, the generation of patient-specific iPS cells could be used to screen new drugs [6]and[7]. However, there are currently several limitations in applying iPS cells clinically. Efficiency of converting somatic cells to iPS cells is still very low. In particular, only approximately 0.1% to 1% of somatic cells experience changes at the transcriptional level and finally become pluripotent stem cells when non-integration approaches are used [8]. Moreover, compared to embryonic stem (ES) cells, the developmental potential and differentiation capacity of iPS cells is significantly reduced and there is increased variability among all iPS cell lines [9]. In mice, only small proportions of these cells are fully reprogrammed based on the most stringent tetraploid complementation assay for evaluating pluripotency [10], [11], [12]and[13]. Therefore, it is necessary to establish a strict molecular standard system to distinguish fully reprogrammed iPS cells from those partially reprogrammed, as we currently lack suitable in vivo pluripotency tests for human iPS cells.

In this review, we mainly focus on recent progress on rodent, non-human primate and human iPS cells, and point out some key questions which need to be addressed in the near future, such as the pluripotency level of human iPS cells and the establishment of a new standard to assess the pluripotency level of human iPS cells.

Takahashi and Yamanaka reprogrammed mouse embryonic fibroblasts by the ectopic expression of four reprogramming factors using retroviral vectors, and finally produced iPS cells which resemble ES cells [1]. This original iPS reprogramming approach used viral vectors, including retrovirus and lentivirus which possess high reprogramming efficiency [14]and[15]. The genome may be mutated by integrating other gene sequences, thus raising concerns on the safety issue. In addition, the insertion of oncogenes, like c-Myc, increases the risk of tumor formation [16]and[17]. Subsequently, several modified methods were used to obtain much safer iPS cells, for instance, piggyBac transposon [18], adenovirus [19], sendai virus [20], plasmid [21], episomal vectors [22] and minicircle vectors [23]. However, the reprogramming efficiency is significantly decreased and it takes longer to reactivate the key pluripotency markers to achieve full reprogramming. Therefore, efficient generation of non-integrated iPS cells by new approaches may promote their clinical application.

Recent studies have described several reprogramming methods using proteins, RNAs and small-molecule compounds to derive safe iPS cells [24], [25]and[26]. Zhou et al. obtained iPS cells induced by recombination of the proteins of the four Yamanaka factors obtained by fusing the C-terminus of the proteins with poly-arginine (11R) [24]. A recent study reported that mouse and human iPS cells can be efficiently generated by miRNA mediated reprogramming [25]. Miyoshi et al. [26] successfully generated iPS cells by direct transfection of human somatic cells using mature miRNA. iPS cells can also be generated by synthetic RNAs, which bypass the innate response to viruses [27]. Recently, Houet et al. [28] showed that pluripotent stem cells can be generated from mouse somatic cells at an efficiency of 0.2% by using a combination of seven small-molecule compounds. Compared to traditional viral methods, the aforementioned approaches can be used to generate qualified iPS cells (Table 1) without the risk of insertional mutagenesis. Nonetheless, some familiar drawbacks exist, such as a longer and less efficient reprogramming process. In other words, what we need to do next is to optimize non-integration induction systems in order to resolve these drawbacks.

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Pluripotency of Induced Pluripotent Stem Cells