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Use Of Induced Pluripotent Stem Cell Models To Elucidate …

Degree Name

Doctor of Philosophy (PhD)

Cell & Molecular Biology

Jean Bennett

Choroideremia (CHM) is a rare monogenic, X-linked recessive inherited retinal degenerative disease caused by mutations in the Rab Escort Protein-1 (REP1) encoding CHM gene. CHM is characterized by childhood-onset night blindness (nyctalopia), progressive peripheral vision loss due to the degeneration of neural retina, RPE and choroid in a peripheral-to-central fashion. Most of CHM mutations are loss-of-function mutations leading to the complete lacking of REP1 protein. However, the primary retinal cell type leading to CHM and molecular mechanism remains unknown in addition to the fact of lacking proper disease models. In this study, we explored the utility of induced pluripotent stem cell-derived models of retinal pigment epithelium (iPSC-RPE) to study disease pathogenesis and a potential gene-based intervention in four different genetically distinct forms of CHM. A number of abnormal cell biologic, biochemical, and physiologic functions were identified in the CHM patient cells. Transduction efficiency testing using 11 recombinant adeno-associated virus (AAV) serotype 1-9, 7m8 and 8b showed a differential cell tropism on iPSC and iPSC-derived RPE. We identified AAV7m8 to be optimal for both delivering transgenes to iPSC-RPEs as well as to appropriate target cells (RPE cells and rod photoreceptors) in the primate retina. To establish the proof of concept of AAV7m8 mediated CHM gene therapy, we developed a AAV7m8.hCHM viral vector, which delivers the human CHM cDNA under control of CMV-enhanced chicken -actin promoter (CA). Delivery of AAV7m8.CMV.CA.hCHM to CHM iPSC-RPEs restored protein prenylation, trafficking and phagocytosis defects. The results confirm that AAV-mediated delivery of the REP1-encoding gene can rescue defects in CHM iPSC-RPE regardless of the type of disease-causing mutation. The results also extend our understanding of mechanisms involved in the pathophysiology of choroideremia.

Duong, Thu Thi, "Use Of Induced Pluripotent Stem Cell Models To Elucidate Retinal Disease Pathogenesis And To Develop Gene-Based Therapies" (2018). Publicly Accessible Penn Dissertations. 3003. https://repository.upenn.edu/edissertations/3003

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Human Embryonic Stem Cells in Development, Volume 129 …

Dr. Brivanlou received his doctoral degree in 1990 from the University of California, Berkeley. He joined Rockefeller in 1994 as assistant professor after postdoctoral work in Douglas Meltons lab at Harvard University. Among his many awards are the Irma T. Hirschl/ Monique Weill-Caulier Trusts Career Scientist Award, the Searle Scholar Award, the James A. Shannon Directors Award from the NIH and the Presidential Early Career Award for Scientists and Engineers. The Brivanlou laboratory has demonstrated that the TGF- pathway plays a central role in inductive interactions leading to the establishment of different neural fates, which begins by the specification of the brain. In studies of frog embryos, Dr. Brivanlou has made several influential discoveries, including the finding that all embryonic cells will develop into nerve cells unless they receive signals directing them toward another fate. A concept, coined the default model of neural induction, postulates that neural fate determination requires the inhibition of an inhibitory signal. His laboratory has contributed to the molecular and biochemical understanding of the TGF- signaling pathway and cross talk with other signaling networks, using comparative studies of frog and mouse embryos and mammalian cell culture. To address whether the default model of neural induction is conserved from amphibians to mammals (and humans in particular), Dr. Brivanlous laboratory was among the first to work directly in hESCs. Dr. Brivanlou and colleagues derived several hESC lines, called RUES1, 2 and 3 (Rockefeller University Embryonic Stem Cell Lines 1, 2 and 3). The RUES lines were among the first 13 hESC lines approved for use in research funded by the National Institutes of Health (NIH), under the NIH Guidelines for Human Stem Cell Research adopted in July 2009 under the Obama administration. Their current work focuses on the molecular dissection of the defining properties of ESCs their capacity for self-renewal and their ability to differentiate into a range of cell types. Dr. Brivanlous overall goal is to use hESCs to study early human embryonic development. Several collaborations with Rockefeller University physics laboratories have provided new insight, from the use of quantum dots for in vivo embryonic imaging (with Albert J. Libchaber) to development of new statistical tools for DNA microarray and high throughput proteomic analysis. Ongoing collaboration with Rockefellers Eric D. Siggia focuses on using a high throughput microfluidic platform to program hESC differentiation toward specific fates by dynamic changes of the signaling landscape and without compromising genetic integrity. Thus, the first steps of stem cell differentiation are being scrutinized using new high-resolution techniques drawn from physics. This data will be organized and developed into a predictive tool to rationally reprogram specialized fates from hESCs.

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Human Embryonic Stem Cells in Development, Volume 129 ...

Reprogrammed stem cells identical to embryonic stem cells

Click on photo (at left) to enlarge Photo:iPS cells feature reprogrammed stem cells: Credit: Moscow Institute of Physics and Technology

Russian researchers have concluded that reprogramming does not create differences between reprogrammed and embryonic stem cells.

Stem cells are specialized,undifferentiated cellsthat can divide and have the remarkable potential to develop into many different cell types in the body during early life and growth. They serve as a sort of internal repair system in many tissues, dividing essentially without limit to replenish other cells. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another more specialized cell type, such as a muscle cell, a red blood cell, or a brain cell. Scientists

distinguish several types ofstem cellspluripotent stem cells can potentially produce any cell in the body. No pluripotent stem cells exist in an adult body, rather they are found naturally in early embryos.

There are two ways to harvest pluripotent stem cells. The first is to extract them from the excess embryos produced duringinvitro fertilization procedures, although this practice is still ethically and technically controversial because it does destroy an embryo that could have been implanted. For this reason, researchers came up with the second way to get pluripotent stem cells reprogramming adult cells.

Reprogramming, the process of turning on genes that are active in a stem cell and turning off genes that are responsible for cell specialization was pioneered by Shinya Yamanaka, who showed that the introduction of four specific proteins essential during early embryonic development could be used to convert adult cells intopluripotent cells. Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon for the discovery that mature stem cells can be reprogrammed to become pluripotent.

Production of iPS cells: Isolate cells from patient; grow in a dish Treat cells with reprogramming Wait a few weeks Pluripotent stem cells Change culture conditions to stimulate cells to differentiate into a variety of cell types blood cells | gut cells | cardio muscle cells Credit: Moscow Institute of Physics and Technology

Thanks to their unique regenerative abilities, stem cells offer potential for treating any disease. For example, there have been cases of transplanting retinal pigment epithelium and spine cells from stem cells. Another experiment showed that stem cells were able to regenerate teeth in mice. Reprogramming holds great potential for new medical applications, since reprogrammed pluripotent stem cells (or induced pluripotent stem cells) can be made from a patients own cells instead of using pluripotent cells from embryos.

However, the extent of the similarity between induced pluripotent stem cells and humanembryonic stem cellsremains unclear. Recent studies highlighted significant differences between these two types of stem cells, although only a limited number of cell lines of different origins were analyzed.

Researchers compared induced pluripotent stem cell (iPSC) lines reprogrammed from adult cell types that were previously differentiated from embryonic stem cells. All these cells were isogenic, meaning they all had the same gene set.

Scientists analyzed the transcriptome the set of all products encoded, synthesized and used in a cell. Moreover, they elicited methylated DNA areas, because methylation plays a critical role in cell specialization. Comprehensive studies of changes in the gene activity regulation mechanism showed similarities between reprogrammed and embryonic stem cells. In addition, researchers produced a list of the activity of 275 key genes that can present reprogramming results.

Researchers studied three types of adult cells fibroblasts, retinal pigment epithelium andneural cells, all of which consist of the same gene set; but a chemical modification (e.g. methylation) combined with other changes determines which part of DNA will be used for product synthesis.

Scientists concluded that the type of adult cells that were reprogrammed and the process of reprogramming did not leave any marks. Differences between cells that did occur were thought to be the result of random factors.

We defined the best induced pluripotent stem cells line concept, says Dmitry Ischenko, MIPT Ph.D. and Institute of Physical Chemical Medicine researcher.

The minimum number of iPSC clones that would be enough for at least one to be similar to embryonic pluripotent cells with 95 percent confidence is five.

Clearly, no one is going to convert embryonic stem cells into neurons and reprogram them into induced stem cells. Such a process would be too time-consuming and expensive. This experiment simulated the reprogramming of a patientsadult cellsinto inducedpluripotent stem cellsfor further medical use, and even though the reprogramming paper, published in the journal Cell Cycle, does not currently propose a method of organ growth in vitro, it is an important step in the right direction. Both induced pluripotent cells and embryonic stem cells can help researchers understand how specialized cells develop from pluripotent cells. In the future, they may also provide an unlimited supply of replacement cells and tissues that can benefit many patients with diseases that are currently untreatable.

The study, titled, An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion, concluded that reprogramming does not create differences between reprogrammed and embryonic stem cells, involved researchers from the Vavilov Institute of General Genetics, Research Institute of Physical Chemical Medicine, and the Moscow Institute of Physics and Technology (MIPT).

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Reprogrammed stem cells identical to embryonic stem cells

Embryonic Stem Cell Protocols by Kursad Turksen | Waterstones

Now in two volumes, this completely updated and expanded edition of Embryonic Stem Cells: Methods and Protocols provides a diverse collection of readily reproducible cellular and molecular protocols for the manipulation of nonhuman embryonic stem cells. Volume two, Embryonic Stem Cell Protocols: Differentiation Models, Second Edition, covers state-of-the-art methods for deriving many types of differentiating cells from ES cells. The first volume, Embryonic Stem Cell Protocols: Isolation and Characterization, Second Edition, provides a diverse collection of readily reproducible cellular and molecular protocols for the isolation, maintenance, and characterization of embryonic stem cells. Together, the two volumes illuminate for both novices and experts our current understanding of the biology of embryonic stem cells and their utility in normal tissue homeostasis and regenerative medicine applications.

Publisher: Humana Press Inc. ISBN: 9781617377778 Number of pages: 456 Weight: 700 g Dimensions: 229 x 152 x 27 mm Edition: Softcover reprint of hardcover 2nd ed. 2006

"...elegantly introduces tremendous methods and protocols in ES studies...one of the most useful books that I have ever read in this field..." -Cell Biology International

"...highly valuable for any scientist who wants to make a start in the exciting field but also for experienced ES cell researchers who want to widen their repertoire" -Diabetologia

"...a very informative resource for any developmental or cell biologist with an interest in developments and prospects of ES cell research" -Molecular Biotechnology

"...a useful companion volume to other more specialized ES cell books..." -Nature Cell Biology

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Embryonic Stem Cell Protocols by Kursad Turksen | Waterstones

Stem Cell Research | The Center for Bioethics & Human Dignity

Stem cell research has been touted as a highly promising avenue for the treatment of disease and injury. Embryonic stem cells (ESC) have the ability to differentiate into the more than 200 different cell types in the human body. While these controversial cells have been promoted as more promising for the treatment of disease, this research involves the destruction of embryos, and thus makes it unethical from CBHD's perspective. Furthermore, despite all of the early claims of potential ESC researchhas faced significanttechnical hurdles. Adult stem cells are found in several human tissues (e.g., bone marrow and umbilical cord blood), and in contrast to embryonic stem cells do not raise the same kind of moral concerns and have provided a number of successful treatments and therapies. Recent advances in this field also include the discovery and development of induced pluripotent stem cells (iPS or iPSCs) and direct cell reprogramming, both of which hold significant promise for the understanding and treatment of disease and avoid the ethical concerns of embryonic stem cell research raised by the destruction of human embryos. Other ethical considerations regarding stem cell research include the potential use of human pluripotent stem cells in animals as well as the potential creation of human gametes or embryos from stem cells. Stem cell research falls under the broader category of biotechnology.

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Stem Cell Research | The Center for Bioethics & Human Dignity

Stem Cell Research | NWABR.ORG

This unit, which was designed by teachers in conjunction with scientists, ethicists, and curriculum developers, explores the scientific and ethical issues involved in stem cell research. The unit begins with an exploration of planaria as a model organism for stem cell research. Next, students identify stages in the development of human embryos and compare the types and potency of stem cells. Students learn about a variety of techniques used for obtaining stem cells and the scientific and ethical implications of those techniques. While exploring the ethics of stem cell research, students will develop an awareness of the many shades of gray that exist among positions of stakeholders in the debate. Students will be provided an opportunity to become familiar with policies and regulations for stem cell research that are currently in place in the United States, the issues regarding private and public funding, and the implications for treatment of disease and advancement of scientific knowledge.

The unit culminates with students developing a position on embryonic stem cell research through the use of a Decision-Making Framework. Two culminating assessments are offered: In the individual assessment, students write a letter to the President or the Presidents Bioethics Committee describing their position and recommendations; In the group assessment, students develop a proposal for NIH funding to research treatment for a chosen disease using either embryonic or 'adult' stem cells.

The complete Stem Cell Curriculum is now available free for download from the Lessons page.

In order for us to measure how our curriculum resources are being used, please take a moment tocontact us.

We also welcome feedback about our Stem Cell Curriculum. We will not share your contact information with anyone.

Links

This unit, which was designed by teachers in conjunction with scientists, ethicists, and curriculum developers, explores the scientific and ethical issues involved in stem cell research. The unit begins with an exploration of planaria as a model organism for stem cell research. Next, students identify stages in the development of human embryos and compare the types and potency of stem cells. Students learn about a variety of techniques used for obtaining stem cells and the scientific and ethical implications of those techniques. While exploring the ethics of stem cell research, students will develop an awareness of the many shades of gray that exist among positions of stakeholders in the debate. Students will be provided an opportunity to become familiar with policies and regulations for stem cell research that are currently in place in the United States, the issues regarding private and public funding, and the implications for treatment of disease and advancement of scientific knowledge.

The unit culminates with students developing a position on embryonic stem cell research through the use of a Decision-Making Framework. Two culminating assessments are offered: In the individual assessment, students write a letter to the President or the Presidents Bioethics Committee describing their position and recommendations; In the group assessment, students develop a proposal for NIH funding to research treatment for a chosen disease using either embryonic or 'adult' stem cells.

The complete Stem Cell Curriculum is now available free for download. In order for us to measure how our curriculum resources are being used, we request that you please complete the brief information form before being directed to the download page. We will not share your contact information with anyone, although we may contact you in the future in order to determine how our materials are being used.

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Stem Cell Research | NWABR.ORG

Stem Cell Research Program Grants portal.ct.gov | Stem …

Connecticut Stem Cell Research Grants-in-Aid Program

The Connecticut Stem Cell Research Grants-in-Aid Program was established by the Connecticut General Assembly in June 2005 when it passed Connecticut General Statutes 19a-32d through 19a-32g. This legislation appropriates $20 million dollars to support embryonic and human adult stem cell research through June 30, 2007. In addition, for each of the fiscal years ending June 30, 2008 through June 30, 2015, the legislation specifies that an additional $10 million dollars should be disbursed to support additional research. In total, at least $100 million in public support will be available over the next ten years for stem cell research.

Lay Summary Example

Below is an example of a lay summary excerpt from a technical report required of all grantees that meets the expectations of the Stem Cell Research Advisory Committee:

5. Detailed lay language summary:

There is great promise in embryonic stem cell-based therapies to treat a variety of neurological disorders. It is key that we understand how the transplanted cells may interact with the host brain to guarantee the safety of this approach. We observe that robust transplants of embryonic stem cell-derived neural progenitors in the hippocampus are richly vascularized, associated with multiple blood vessels. In addition, the transplanted cells can migrate on these blood vessels some distance away from the initial transplant site. We are now studying how interactions with the blood vessels may nurture the transplant and support its successful integration into the host. We are also examining the factors that might promote or inhibit the migration of transplanted cells on the surface of existing blood vessels. This interaction could be used to target grafted cells to a specific site. Alternatively this could be a dangerous process we would like to block, as it could lead to cells present in undesirable places.

Significance of recent findings: When embryonic stem cell-derived neural progenitors are transplanted to the central nervous system, the general expectation is that they will remain where transplanted, or perhaps migrate short distances. Our observation that these cells can migrate on blood vessels long distances sets up a red flag: cells may well end up a great distance from where they were intended to be. By understanding the molecular basis for this migration, we hope to be able to control it, specifically inhibit it when the desire is to keep a transplant in place. Alternatively, it may be desirable to use this blood vessel highway to target cells to specific distant sites.

Frequently Asked Questions

How did Connecticuts Stem Cell Research Program come about?

The Connecticut Stem Cell Research Grant Project is the direct result of legislation passed by the General Assembly in 2005 (Connecticut General Statutes 19a-32d through 19a-32g.). This legislation provides public funding in support of stem cell research on embryonic and human adult stem cells. This legislation also bans the cloning of human beings in Connecticut.

Back to Questions

What kinds of research will be eligible for funding?

The Stem Cell Research Fund supports embryonic and human adult stem cell research, including basic research to determine the properties of stem cells.

Back to Questions

Where is the money coming from for this research?

Stem cell research fundscome from the Stem Cell Research Fund. This Fund will receive a total of $100 million dollars of state money over ten years. The General Assembly had set aside $20 million of state money for the purpose of stem cell research through June 2007. An additional $10 million dollars a year over the subsequent eight years will come from the Connecticut Tobacco Settlement Fund. The Stem Cell Research Fund may also contain any funds received from any public or private contributions, gifts, grants, donations or bequests.

Back to Questions

Who oversees the Stem Cell Research Fund?

The Commissioner of the State Department of Public Health (DPH) may make grants-in-aid from the fund. The Connecticut Stem Cell Research Advisory Committee (Advisory Committee), a legislatively appointed committee established by Connecticut General Statutes 19a-32d through 19a-32g, directs the Commissioner with respect to the awarding of grants-in-aid, and develops the stem cell research application process. The Stem Cell Research Advisory Committee is also required to keep the Governor and the General Assembly apprised of the current status of stem cell research in Connecticut through annual reports commencing June 2007.

The legislation further established a Connecticut Stem Cell Research Peer Review Committee (Peer Review Committee) to review all applications with respect to the scientific and ethical meritsand to make recommendations to the Advisory Committee and the Commissioner of DPH.

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How are the members of the Stem Cell Research Advisory Committee determined?

The Stem Cell Research Advisory Committee is made up of 17 members. By statute, the Advisory Committee is chaired by the Commissioner of the Connecticut Department of Public Health (DPH). Other members of the committee are appointed by the Governor and by various leaders of the General Assembly from the fields of stem cell research, stem cell investigation, bioethics, embryology, genetics, cellular biology and business. Committee members commit to a two-year or four-year term of service.

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Who evaluates the merits of the grant applications and decides how the grants are distributed?

The Stem Cell Research Peer Review Committee reviews all grant applications for scientific and ethical merit, guided by the National Academies Guidelines for Human Embryonic Stem Cell Research. The Stem Cell Research Peer Review Committee makes its recommendations on grants to the Stem Cell Research Advisory Committee for consideration. The members of the Stem Cell Peer Review Committee must have demonstrated and practical knowledge, understanding and experience of the ethical and scientificimplications of embryonic and adult stem cell research. The DPH Commissioner appoints all committee members for either two or four-year terms. The Stem Cell Research Advisory Committee directs the Commissioner of the Department of Public Health with respect to the awarding of grants-in-aid.

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Who may apply for the stem cell research grants?

Any non-profit, tax-exempt academic institution of higher education, any hospital that conducts biomedical research or any entity that conducts biomedical research or embryonic or human adult stem cell research may apply for grants from the Connecticut Stem Cell Research Fund.

Back to Questions

What efforts are being made to assure the people of the state of Connecticut that all committee dealings and any research are ethically conducted?

The State of Connecticut is committed to implementing the Stem Cell Research Program according to the highest ethical and scientific standards, and committed to conducting all business activities in a transparent and consumer friendly manner. Meetings of the committee where decisions are being made will comply with Freedom of Information Act requirements for public meetings and public records. Proceedings of all scheduled meetings of the Advisory Board will be transcribed and made available to the public, and when possible, meetings will be televised via local public access television.

Members of the Stem Cell Research Advisory Committee are considered to be public officials and are subject to state ethics laws, which require full accountability and transparency. Both the Peer Review and Advisory Committees are responsible for overseeing the standards of research funded from this grant program. Reports on scientific progress are required of grant recipients. Annual financial disclosures are required for all members of the Stem Cell Research Advisory Committee.

Back to Questions

Who else is involved with overseeing this project?

The State of Connecticut Department of Public Health, working in conjunction with the legislatively mandated Advisory and Peer Review Committees, is responsible for the overall implementation of the stem cell legislation.Withinthe DPH, the Office of Research and Development is the organizational unit tasked with managing the stem cell research project components.

In addition, the stem cell legislation names Connecticut Innovations as the administrative staff of the Stem Cell Research Advisory Committee, assisting the Advisory Committee in developing and implementing the application process, including application reviews and execution of agreements.

Back to Questions

What is the timeline for the application process?

The Advisory Committee developed and issued the first Request for Proposals on May 10, 2006. As of the July 10, 2006 deadline, 70 applications for public funding were received. Applications were made available for peer review on August 4, 2006.On November 21, 2006, the Stem Cell Research Advisory Committee awarded almost $19.8 million for 21 stem cell research proposals.

The second Request for Proposals was issued on July 25, 2007. As of the November 1, 2007 deadline, 94 applications for public funding were received. The Peer Review Committee completed their review and reported by teleconference on March 5, 2008. On April 1, 2008, the SCRAC awarded $9.84 million for 22 stem cell research projects.

The third Request for Proposals was issued on September 24, 2008. As of the December 8, 2008 deadline, 77 applications for public funding were received. The Peer Review Committee completed their review and reported by teleconference on March 17, 2009. On March 31, 2009, the SCRAC awarded $9.8 million for 24 stem cell research projects.

Back to Questions

Which grant applications received funding in 2006?

An Integrated Approach to Neural Differentiation of Human Embryonic Stem Cells, Yale University, Michael P. Snyder, Principal Investigator, $3,815,476.72

Directing hES Derived Progenitor Cells into Musculoskeletal Lineages, University of Connecticut Health Center and University of Connecticut, David W. Rowe, M. D., Principal Investigator, $3,520,000

Human Embryonic Stem Cell Core Facility at Yale Stem Cell Center, Yale University, Haifan Lin, Principal Investigator, $2,500,000

Human ES Cell Core At University of Connecticut and Wesleyan University, University of Connecticut Health Center, Ren-He Xu, Principal Investigator, $2,500,000

DsRNA and Epigenetic Regulation in Embryonic Stem Cells, University of Connecticut Health Center, Gordon G. Carmichael, $880,000.

Alternative Splicing in Human Embryonic Stem Cells, University of Connecticut Health Center, Brenton R. Graveley, Principal Investigator, $880,000

SMAD4-based ChIP-chip Analysis to Screen Target Genes of BMP and TGF Signaling in Human ES Cells, University of Connecticut Health Center, Ren-He Xu, Principal Investigator, $880,000

Directing Production and Functional Integration of Embryonic Stem Cell-Derived Neural Stem Cells, Wesleyan University, Laura B. Grabel, Principal Investigator, $878,348.24

Role of the Leukemia Gene MKL in Developmental Hematopoiesis Using hES Cells, Yale University, Diane Krause, Principal Investigator, $856,653.72

Migration and Integration of Embryonic Stem Cell Derived Neurons into Cerebral Cortex, University of Connecticut, Joseph LoTurco, Principal Investigator, $561,631.84

Optimizing Axonal Regeneration Using a Polymer Implant Containing hESC-derived Glia, University of Connecticut, Akiko Nishiyama, $529,871.76

Development of Efficient Methods for Reproducible and Inducible Transgene Expression in Human Embryonic Stem Cells, University of Connecticut Health Center, James Li, Principal Investigator, $200,000

Pragmatic Assessment of Epigenetic Drift in Human ES Cell Lines, University of Connecticut, Theodore Rasmussen, Ph.D., Principal Investigator, $200,000

Cell Cycle and Nuclear Reprogramming by Somatic Cell Fusion, University of Connecticut Health Center, Winfried Krueger, Principal Investigator, $200,000

Function of the Fragile X Mental Retardation Protein in Early Human Neural Development, Yale University, Yingqun Joan Huang, Principal Investigator, $200,000

Quantitative Analysis of Molecular Transport and Population Kinetics of Stem Cell Cultivation in a Microfluidic System, University of Connecticut, Tai-His Fan, Principal Investigator, $200,000

Embryonic Stem Cell as a Universal Cancer Vaccine, University of Connecticut Health Center, Bei Liu, Zihai Li, M. D., Principal Investigators, $200,000

Lineage Mapping of Early Human Embryonic Stem Cell Differentiation, University of Connecticut, Craig E. Nelson, $200,000

Directed Isolation of Neuronal Stem Cells from hESC Lines, Yale University School of Medicine, Eleni A. Markakis, Principal Investigator, $184,407

Magnetic Resonance Imaging of Directed Endogenous Neural Progenitor Cell Migration, Yale University School of Medicine, Erik Shapiro, Principal Investigator, $199,975

Generation of Insulin Producing Cells from Human Embryonic Stem Cells, University of Connecticut, Gang Xu, Principal Investigator, $200,000

Back to Questions

Which grant applications received funding in 2008?

Maintaining and Enhancing the Human Embryonic Stem Cell Core at the Yale Stem Cell Center, Yale University Stem Cell Center, New Haven, Haifan Lin, PhD, Principal Investigator, $1,800,000.

Translational Studies in Monkeys of hESCs for Treatment of Parkinsons Disease, Yale University School of Medicine, New Haven, D. Eugene Redmond, Jr., MD, Principal Investigator, $1,120,000.

Production and Validation of Patient-Matched Pluipotent Cells for Improved Cutaneous Repair, University of Connecticut Center of Regenerative Biology, Storrs, Theodore Rasmussen, PhD., Principal Investigator, $634,880.

Directed Differentiation of ESCs into Cochlear Precursors for Transplantation as Treatment of Deafness, University of Connecticut, Storrs, Ben Bahr, PhD, Principal Investigator, $500,000.

Synaptic Replenishment Through Embryonic Stem Cell Derived Neurons in a Transgenic Mouse Model of Alzheimers Disease, University of Connecticut Health Center, Farmington, Nada Zecevic, MD, PhD, Principal Investigator, $499,813.

Tyrosone Phosphorylation Profiles Associated with Self-Renewal and Differentiation of hESC, University of Connecticut Health Center, Farmington, Bruce Mayer, PhD., Principal Investigator, $450,000.

Directed Differentiation of ESCs into Cochlear Precursors for Transplantation as Treatment of Deafness, University of Connecticut Health Center, Farmington, D. Kent Morest, MD, Principal Investigator, $450,000.

Targeting Lineage Committed Stem Cells to Damaged Intestinal Mucosa, University of Connecticut Health Center, Farmington, Daniel W. Rosenberg, PhD., Principal Investigator, $450,000.

Modeling Motor Neuron Degeneration in Spinal Muscular Atrophy Using hESCs, University of Connecticut Health Center, Farmington, Xuejun Li, PhD., Principal Investigator, $450,000.

Human Embryonic and Adult Stem Cell for Vascular Regeneration, Yale University School of Medicine, New Haven, Laura E. Niklason, MD, PhD, $450,000.

Effect of Hypoxia on Neural Stem Cells and the Function in CAN Repair, Yale University, New Haven, Flora M. Vaccarino, Principal Investigator, $449,771.40.

Wnt Signaling and Cardiomyocyte Differentiation from hESCs, Yale University, New Haven, Dianqing Wu, Principal Investigator, $446,818.50.

Flow Cytometry Core for the Study of hESC, University of Connecticut Health Center, Farmington, Hector Leonardo Aguila, PhD., Principal Investigator, $250,000.

Cortical neuronal protection in spinal cord injury following transplantation of dissociated neurospheres derived from human embryonic stem cells, Yale University School of Medicine, New Haven, Masanori Sasaki, MD, PhD, Principal Investigator, $200,000.

Molecular Control of Pluripotency in Human Embryonic Stem Cell, Yale Stem Cell Center, New Haven, Natalia Ivanova, Principal Investigator, $200,000.

Cytokine-induced Production of Transplantable Hematopoietic Stem Cells from Human ES Cells, University of Connecticut Health Center, Farmington, Laijun Lai, PhD, Principal Investigator, $200,000.

Functional Use of Embryonic Stem Cells for Kidney Repair, Yale University, New Haven, Lloyd G. Cantley, Principal Investigator, $200,000.

VRK-1-mediated Regulation of p53 in the Human ES Cell Cycle, Yale University, New Haven, Valerie Reinke, Principal Investigator, $200,000.

Definitive Hematopoitic Differentiation of hESCs under Feeder-Free and Serum-Free Conditions, Yale University, Caihong Qiu, PhD, Principal Investigator, $200,000.

Differentiation of hESC Lines to Neural Crest Derived Trabecular Meshwork Like Cells Implications in Glaucoma, University of Connecticut Health Center, Farmington, Dharamainder Choudhary, PhD., Principal Investigator, $200,000.

The Role of the piRNA Pathway in Epigenetic Regulation of hESCs, Yale University, New Haven, Qiaoqiao Wang, PhD., Principal Investigator, $200,000.

Early Differentiation Markers in hESCs: Identification and Characterization of Candidates, University of Connecticut Center for Regenerative Biology, Storrs, Mark G. Carter, PhD., Principal Investigator, $200,000.

Regulation hESC-dervied Neural Stem Cells by Notch Signaling, Yale University, New Haven, Joshua Breunig, MD, Principal Investigator, $188,676.

Back to Questions

Which grant applications received funding in 2009?

Continuing and Enhancing the UCONN-Wesleyan Stem Cell Core, University of Connecticut Stem Cell Center, Farmington, Ren-He Xu, MD, PhD, Principal Investigator, $1,900,000.00.

Williams Syndrome Associated TFII-I Factor and Epigenetic Marking-Out in hES and Induced Pluripotent Stem Cells, University of Connecticut Health Center, Farmington, Dashzeveg Bayarsaihan, PhD., Principal Investigator, $500,000.00.

Cellular transplantation of neural progenitors derived from human embryonic stem cells to remyelinate the nonhuman primate spinal cord, Yale University, New Haven, Jeffrey Kocsis, PhD., Principal Investigator, $500,000.00.

Mechanisms of Stem Cell Homing to the Injured Heart, University of Connecticut Health Center, Linda Shapiro, PhD., Principal Investigator, $500,000.00.

Originally posted here: Stem Cell Research Program Grants portal.ct.gov

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Stem Cell Research Program Grants portal.ct.gov | Stem ...

Stem Cell Treatment – Philadelphia Bala Cynwyd, PA: World …

Stem Cell Treatment in Philadelphia, PA

To treat joint and musculoskeletal system injuries, or if you suffer from chronic conditions affecting the joints or bones, there are options other than surgery to treat the issues. At World Wellness Health Institute, Dr. Daniel Lebowitz uses stem cell therapy on people living in and around Bala Cynwyd and Philadelphia, PA, who have chronic conditions and are in need of advanced treatment to heal injuries and relieve pain associated with injuries, arthritis, and other conditions.

What is Stem Cell Therapy?

Stem cell therapy is a cutting-edge treatment used in orthopedic injuries and other chronic conditions that affect the musculoskeletal system, such as arthritis and neck, back and joint pain. It is now a consideration for treatment instead of surgery. With stem cell therapy, many patients regain full function of the treated area without a lengthy recovery period, unlike with surgery. This type of stem cell therapy is FDA approved and takes stem cells from the patients own adipose tissue. This tissue (fat tissue) is rich in stem cells, primarily mesenchymalstem cells.

Benefits of Stem Cell Treatment

Stem cell injections are used primarily to relieve pain in the joints as they provide the following benefits:

How Does Stem Cell Therapy Work?

With stem cell therapy, fat is harvested in a process called lipoaspiration. The targeted area is numbed with a local anesthetic, then a small needle just a tad larger than a hypodermic needle is injected into the skin to remove about 10 to 20ccs of adipose tissue (fat). Once the fat is removed, it is run through another process called sterile gravity method and combined with high-density PRP (platelet-rich plasma) and injected into the site where the pain occurs. Stem cells stimulate the healing process providing several functions. They can differentiate or even change into the type of cells needed, whether its a ligament, tendon, bone or cartilage, at the injection site to start healing. We prescribe oral anti-anxiety medicine and pain medicines that you can take prior to the procedure. If necessary, Dr. Lebowitz may use local anesthetic to numb the injection sites. You typically need only one treatment but, if necessary, a follow-up treatment may be performed several weeks later.

Stem Cell Therapy Preparation

Much of the preparation for stem cell therapy involves determining if the patient is a good candidate for this type of treatment. It is necessary to stop taking any medications and/or supplements that may thin the blood at least one week prior to the treatment, as well as avoid smoking.

Stem Cell Therapy Recovery

Stem cell therapy treatment is not a painful procedure, as oral pain relievers and local anesthetics are used to numb the treatment areas. It is okay to return to work immediately after the procedure, as well as participate in any activities. Most patients notice improvement after two weeks and continue to experience improvement over the next few months following the treatment.

How Much Does Stem Cell Therapy Cost?

Stem cell therapy is a relatively new procedure and varies in cost depending on the area to be treated, how many treatments may be required and if it is done at the same time another treatment is performed. We can discuss the cost with you during your consultation, in addition to going over our payment options. We do offer financing through CareCredit.

Is Stem Cell Therapy Right for Me?

If you suffer from osteoarthritis or an injury to the knee, back, neck or other joint, stem cell therapy may be right for you. Stem cell therapy is an alternative to invasive surgery when the injured area is not fully collapsed.

Stem Cell Therapy Consultation

During your consultation to determine if you are a candidate for stem cell therapy, it is necessary for Dr. Lebowitz to examine and evaluate the area of your pain, as well as determine the root cause of the pain. Additionally, he will go over your current health, medical history, and lifestyle in terms of diet, exercise, and more. If you have any questions, he answers them in detail so that you fully understand the treatment plan.

If you are experiencing pain in any joint or other part of the musculoskeletal system as a result of an injury or chronic health condition, stem cell therapy offered at World Wellness Health Institute may be the solution. Dr. Daniel Lebowitz offers several treatments for musculoskeletal therapy to residents in Bala Cynwyd, Philadelphia and the surrounding areas of Pennsylvania. Contact ustoday!

*Individual results may vary

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Wisconsin Stem Cell Clinic

Umbilical cord cells include stem cells, growth factors and a range of other beneficial proteins and compounds. We use blood from the umbilical cord which has been purified to get rid of any harmful substances that might cause rejection of the treatment by your body. We inject the treated cord blood into the affected area, where the various active compounds found in cord cells go to work immediately to begin inflammation reduction and the promotion of healthy cell division and renewal. Some of the active compounds at work include VEGF (Vascular Endothelial Growth Factor), IL-LRA (Interleukin-1, a receptor antagonist, stem cell factors (SCF), FGF-2 (Fibroblast Growth Factor-2) and Transforming Growth Factor-beta (TGF-beta). Each of these compounds has a slightly different effect, but the net result is that the damaged cells in your joints are given the ingredients they need to kick-start healthy renewal and regeneration. The injection changes the chemistry inside the joint, creating a healthier environment that encourages positive, healing changes to take place. A better blood supply to the area, a reduction in damaging chronic inflammation and stimulation of healthy tissue growth are all typical consequences of the minimally invasive stem cell treatments we provide. By using umbilical cord cells in this way, its possible to transform joint therapy into a holistic healing process that prompts the body to enhance its own regenerative efforts. This results in a natural process of joint health improvement in the weeks or months following the injection.

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Wisconsin Stem Cell Clinic

stem cell | Definition, Types, Uses, Research, & Facts …

Stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There is great interest in stem cells because they have potential in the development of therapies for replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells.

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cardiovascular disease: Cardiac stem cells

Cardiac stem cells, which have the ability to differentiate (specialize) into mature heart cells and therefore could be used to repair damaged or diseased heart tissue, have garnered significant interest in the development of treatments for heart disease and cardiac defects. Cardiac stem

Embryonic stem cells (often referred to as ES cells) are stem cells that are derived from the inner cell mass of a mammalian embryo at a very early stage of development, when it is composed of a hollow sphere of dividing cells (a blastocyst). Embryonic stem cells from human embryos and from embryos of certain other mammalian species can be grown in tissue culture.

The most-studied embryonic stem cells are mouse embryonic stem cells, which were first reported in 1981. This type of stem cell can be cultured indefinitely in the presence of leukemia inhibitory factor (LIF), a glycoprotein cytokine. If cultured mouse embryonic stem cells are injected into an early mouse embryo at the blastocyst stage, they will become integrated into the embryo and produce cells that differentiate into most or all of the tissue types that subsequently develop. This ability to repopulate mouse embryos is the key defining feature of embryonic stem cells, and because of it they are considered to be pluripotentthat is, able to give rise to any cell type of the adult organism. If the embryonic stem cells are kept in culture in the absence of LIF, they will differentiate into embryoid bodies, which somewhat resemble early mouse embryos at the egg-cylinder stage, with embryonic stem cells inside an outer layer of endoderm. If embryonic stem cells are grafted into an adult mouse, they will develop into a type of tumour called a teratoma, which contains a variety of differentiated tissue types.

Mouse embryonic stem cells are widely used to create genetically modified mice. This is done by introducing new genes into embryonic stem cells in tissue culture, selecting the particular genetic variant that is desired, and then inserting the genetically modified cells into mouse embryos. The resulting chimeric mice are composed partly of host cells and partly of the donor embryonic stem cells. As long as some of the chimeric mice have germ cells (sperm or eggs) that have been derived from the embryonic stem cells, it is possible to breed a line of mice that have the same genetic constitution as the embryonic stem cells and therefore incorporate the genetic modification that was made in vitro. This method has been used to produce thousands of new genetic lines of mice. In many such genetic lines, individual genes have been ablated in order to study their biological function; in others, genes have been introduced that have the same mutations that are found in various human genetic diseases. These mouse models for human disease are used in research to investigate both the pathology of the disease and new methods for therapy.

Extensive experience with mouse embryonic stem cells made it possible for scientists to grow human embryonic stem cells from early human embryos, and the first human stem cell line was created in 1998. Human embryonic stem cells are in many respects similar to mouse embryonic stem cells, but they do not require LIF for their maintenance. The human embryonic stem cells form a wide variety of differentiated tissues in vitro, and they form teratomas when grafted into immunosuppressed mice. It is not known whether the cells can colonize all the tissues of a human embryo, but it is presumed from their other properties that they are indeed pluripotent cells, and they therefore are regarded as a possible source of differentiated cells for cell therapythe replacement of a patients defective cell type with healthy cells. Large quantities of cells, such as dopamine-secreting neurons for the treatment of Parkinson disease and insulin-secreting pancreatic beta cells for the treatment of diabetes, could be produced from embryonic stem cells for cell transplantation. Cells for this purpose have previously been obtainable only from sources in very limited supply, such as the pancreatic beta cells obtained from the cadavers of human organ donors.

The use of human embryonic stem cells evokes ethical concerns, because the blastocyst-stage embryos are destroyed in the process of obtaining the stem cells. The embryos from which stem cells have been obtained are produced through in vitro fertilization, and people who consider preimplantation human embryos to be human beings generally believe that such work is morally wrong. Others accept it because they regard the blastocysts to be simply balls of cells, and human cells used in laboratories have not previously been accorded any special moral or legal status. Moreover, it is known that none of the cells of the inner cell mass are exclusively destined to become part of the embryo itselfall of the cells contribute some or all of their cell offspring to the placenta, which also has not been accorded any special legal status. The divergence of views on this issue is illustrated by the fact that the use of human embryonic stem cells is allowed in some countries and prohibited in others.

In 2009 the U.S. Food and Drug Administration approved the first clinical trial designed to test a human embryonic stem cell-based therapy, but the trial was halted in late 2011 because of a lack of funding and a change in lead American biotech company Gerons business directives. The therapy to be tested was known as GRNOPC1, which consisted of progenitor cells (partially differentiated cells) that, once inside the body, matured into neural cells known as oligodendrocytes. The oligodendrocyte progenitors of GRNOPC1 were derived from human embryonic stem cells. The therapy was designed for the restoration of nerve function in persons suffering from acute spinal cord injury.

Embryonic germ (EG) cells, derived from primordial germ cells found in the gonadal ridge of a late embryo, have many of the properties of embryonic stem cells. The primordial germ cells in an embryo develop into stem cells that in an adult generate the reproductive gametes (sperm or eggs). In mice and humans it is possible to grow embryonic germ cells in tissue culture with the appropriate growth factorsnamely, LIF and another cytokine called fibroblast growth factor.

Some tissues in the adult body, such as the epidermis of the skin, the lining of the small intestine, and bone marrow, undergo continuous cellular turnover. They contain stem cells, which persist indefinitely, and a much larger number of transit amplifying cells, which arise from the stem cells and divide a finite number of times until they become differentiated. The stem cells exist in niches formed by other cells, which secrete substances that keep the stem cells alive and active. Some types of tissue, such as liver tissue, show minimal cell division or undergo cell division only when injured. In such tissues there is probably no special stem-cell population, and any cell can participate in tissue regeneration when required.

The epidermis of the skin contains layers of cells called keratinocytes. Only the basal layer, next to the dermis, contains cells that divide. A number of these cells are stem cells, but the majority are transit amplifying cells. The keratinocytes slowly move outward through the epidermis as they mature, and they eventually die and are sloughed off at the surface of the skin. The epithelium of the small intestine forms projections called villi, which are interspersed with small pits called crypts. The dividing cells are located in the crypts, with the stem cells lying near the base of each crypt. Cells are continuously produced in the crypts, migrate onto the villi, and are eventually shed into the lumen of the intestine. As they migrate, they differentiate into the cell types characteristic of the intestinal epithelium.

Bone marrow contains cells called hematopoietic stem cells, which generate all the cell types of the blood and the immune system. Hematopoietic stem cells are also found in small numbers in peripheral blood and in larger numbers in umbilical cord blood. In bone marrow, hematopoietic stem cells are anchored to osteoblasts of the trabecular bone and to blood vessels. They generate progeny that can become lymphocytes, granulocytes, red blood cells, and certain other cell types, depending on the balance of growth factors in their immediate environment.

Work with experimental animals has shown that transplants of hematopoietic stem cells can occasionally colonize other tissues, with the transplanted cells becoming neurons, muscle cells, or epithelia. The degree to which transplanted hematopoietic stem cells are able to colonize other tissues is exceedingly small. Despite this, the use of hematopoietic stem cell transplants is being explored for conditions such as heart disease or autoimmune disorders. It is an especially attractive option for those opposed to the use of embryonic stem cells.

Bone marrow transplants (also known as bone marrow grafts) represent a type of stem cell therapy that is in common use. They are used to allow cancer patients to survive otherwise lethal doses of radiation therapy or chemotherapy that destroy the stem cells in bone marrow. For this procedure, the patients own marrow is harvested before the cancer treatment and is then reinfused into the body after treatment. The hematopoietic stem cells of the transplant colonize the damaged marrow and eventually repopulate the blood and the immune system with functional cells. Bone marrow transplants are also often carried out between individuals (allograft). In this case the grafted marrow has some beneficial antitumour effect. Risks associated with bone marrow allografts include rejection of the graft by the patients immune system and reaction of immune cells of the graft against the patients tissues (graft-versus-host disease).

Bone marrow is a source for mesenchymal stem cells (sometimes called marrow stromal cells, or MSCs), which are precursors to non-hematopoietic stem cells that have the potential to differentiate into several different types of cells, including cells that form bone, muscle, and connective tissue. In cell cultures, bone-marrow-derived mesenchymal stem cells demonstrate pluripotency when exposed to substances that influence cell differentiation. Harnessing these pluripotent properties has become highly valuable in the generation of transplantable tissues and organs. In 2008 scientists used mesenchymal stem cells to bioengineer a section of trachea that was transplanted into a woman whose upper airway had been severely damaged by tuberculosis. The stem cells were derived from the womans bone marrow, cultured in a laboratory, and used for tissue engineering. In the engineering process, a donor trachea was stripped of its interior and exterior cell linings, leaving behind a trachea scaffold of connective tissue. The stem cells derived from the recipient were then used to recolonize the interior of the scaffold, and normal epithelial cells, also isolated from the recipient, were used to recolonize the exterior of the trachea. The use of the recipients own cells to populate the trachea scaffold prevented immune rejection and eliminated the need for immunosuppression therapy. The transplant, which was successful, was the first of its kind.

Research has shown that there are also stem cells in the brain. In mammals very few new neurons are formed after birth, but some neurons in the olfactory bulbs and in the hippocampus are continually being formed. These neurons arise from neural stem cells, which can be cultured in vitro in the form of neurospheressmall cell clusters that contain stem cells and some of their progeny. This type of stem cell is being studied for use in cell therapy to treat Parkinson disease and other forms of neurodegeneration or traumatic damage to the central nervous system.

Following experiments in animals, including those used to create Dolly the sheep, there has been much discussion about the use of somatic cell nuclear transfer (SCNT) to create pluripotent human cells. In SCNT the nucleus of a somatic cell (a fully differentiated cell, excluding germ cells), which contains the majority of the cells DNA (deoxyribonucleic acid), is removed and transferred into an unfertilized egg cell that has had its own nuclear DNA removed. The egg cell is grown in culture until it reaches the blastocyst stage. The inner cell mass is then removed from the egg, and the cells are grown in culture to form an embryonic stem cell line (generations of cells originating from the same group of parent cells). These cells can then be stimulated to differentiate into various types of cells needed for transplantation. Since these cells would be genetically identical to the original donor, they could be used to treat the donor with no problems of immune rejection. Scientists generated human embryonic stem cells successfully from SCNT human embryos for the first time in 2013.

While promising, the generation and use of SCNT-derived embryonic stem cells is controversial for several reasons. One is that SCNT can require more than a dozen eggs before one egg successfully produces embryonic stem cells. Human eggs are in short supply, and there are many legal and ethical problems associated with egg donation. There are also unknown risks involved with transplanting SCNT-derived stem cells into humans, because the mechanism by which the unfertilized egg is able to reprogram the nuclear DNA of a differentiated cell is not entirely understood. In addition, SCNT is commonly used to produce clones of animals (such as Dolly). Although the cloning of humans is currently illegal throughout the world, the egg cell that contains nuclear DNA from an adult cell could in theory be implanted into a womans uterus and come to term as an actual cloned human. Thus, there exists strong opposition among some groups to the use of SCNT to generate human embryonic stem cells.

Due to the ethical and moral issues surrounding the use of embryonic stem cells, scientists have searched for ways to reprogram adult somatic cells. Studies of cell fusion, in which differentiated adult somatic cells grown in culture with embryonic stem cells fuse with the stem cells and acquire embryonic stem-cell-like properties, led to the idea that specific genes could reprogram differentiated adult cells. An advantage of cell fusion is that it relies on existing embryonic stem cells instead of eggs. However, fused cells stimulate an immune response when transplanted into humans, which leads to transplant rejection. As a result, research has become increasingly focused on the genes and proteins capable of reprogramming adult cells to a pluripotent state. In order to make adult cells pluripotent without fusing them to embryonic stem cells, regulatory genes that induce pluripotency must be introduced into the nuclei of adult cells. To do this, adult cells are grown in cell culture, and specific combinations of regulatory genes are inserted into retroviruses (viruses that convert RNA [ribonucleic acid] into DNA), which are then introduced to the culture medium. The retroviruses transport the RNA of the regulatory genes into the nuclei of the adult cells, where the genes are then incorporated into the DNA of the cells. About 1 out of every 10,000 cells acquires embryonic stem cell properties. Although the mechanism is still uncertain, it is clear that some of the genes confer embryonic stem cell properties by means of the regulation of numerous other genes. Adult cells that become reprogrammed in this way are known as induced pluripotent stem cells (iPS).

Similar to embryonic stem cells, induced pluripotent stem cells can be stimulated to differentiate into select types of cells that could in principle be used for disease-specific treatments. In addition, the generation of induced pluripotent stem cells from the adult cells of patients affected by genetic diseases can be used to model the diseases in the laboratory. For example, in 2008 researchers isolated skin cells from a child with an inherited neurological disease called spinal muscular atrophy and then reprogrammed these cells into induced pluripotent stem cells. The reprogrammed cells retained the disease genotype of the adult cells and were stimulated to differentiate into motor neurons that displayed functional insufficiencies associated with spinal muscular atrophy. By recapitulating the disease in the laboratory, scientists were able to study closely the cellular changes that occurred as the disease progressed. Such models promise not only to improve scientists understanding of genetic diseases but also to facilitate the development of new therapeutic strategies tailored to each type of genetic disease.

In 2009 scientists successfully generated retinal cells of the human eye by reprogramming adult skin cells. This advance enabled detailed investigation of the embryonic development of retinal cells and opened avenues for the generation of novel therapies for eye diseases. The production of retinal cells from reprogrammed skin cells may be particularly useful in the treatment of retinitis pigmentosa, which is characterized by the progressive degeneration of the retina, eventually leading to night blindness and other complications of vision. Although retinal cells also have been produced from human embryonic stem cells, induced pluripotency represents a less controversial approach. Scientists have also explored the possibility of combining induced pluripotent stem cell technology with gene therapy, which would be of value particularly for patients with genetic disease who would benefit from autologous transplantation.

Researchers have also been able to generate cardiac stem cells for the treatment of certain forms of heart disease through the process of dedifferentiation, in which mature heart cells are stimulated to revert to stem cells. The first attempt at the transplantation of autologous cardiac stem cells was performed in 2009, when doctors isolated heart tissue from a patient, cultured the tissue in a laboratory, stimulated cell dedifferentiation, and then reinfused the cardiac stem cells directly into the patients heart. A similar study involving 14 patients who underwent cardiac bypass surgery followed by cardiac stem cell transplantation was reported in 2011. More than three months after stem cell transplantation, the patients experienced a slight but detectable improvement in heart function.

Patient-specific induced pluripotent stem cells and dedifferentiated cells are highly valuable in terms of their therapeutic applications because they are unlikely to be rejected by the immune system. However, before induced pluripotent stem cells can be used to treat human diseases, researchers must find a way to introduce the active reprogramming genes without using retroviruses, which can cause diseases such as leukemia in humans. A possible alternative to the use of retroviruses to transport regulatory genes into the nuclei of adult cells is the use of plasmids, which are less tumourigenic than viruses.

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