Proliferation and Potential of Neural and Retinal Stem Cells

Proliferation and Potential of Neural and Retinal Stem Cells
Author: Laura Donaldson
Publisher:
Total Pages: 610
Release: 2011
Genre:
ISBN: 9780494781692

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The term "stem cell" is often broadly applied to a range of cell types that are relatively undifferentiated and have some capacity for proliferation. In this thesis, I employ a strict definition of stem cells as cells that are capable of both self-renewal and multilineage differentiation. These properties are tested in single precursor cells from the forebrain and its derivative, the retina, using clonal assays. Poor survival is a common problem in single cell cultures, and I show that low oxygen dramatically improves viability in neural stem cells clonally derived from mouse embryonic stem cells, as well as in cultured forebrain neural stem cells. Caspase-dependent and apoptosis-inducing factor-dependent cell death pathways were found to be differentially influenced in low oxygen culture of early, primitive and later, definitive neural stem cells. I isolate precursors from 2 separate regions of the adult mouse forebrain, the lateral ventricle and the hippocampus and argue that only cells resident in the lateral ventricle can be classified as stem cells while the hippocampus contains restricted progenitor cells. Unlike neural stem cells, the very existence of retinal precursors in the adult mammal is controversial. I investigate methods to prospectively identify a rare stem cell population in the pigmented ciliary epithelium of the adult mouse eye and show that, although this population intrinsically gives rise to all retinal cell types, cells can be directed specifically towards a photoreceptor fate by the addition of exogenous factors to the culture media. Pigmentation of retinal stem cells is used as a convenient marker to isolate a retinal stem cell from human embryonic stem cells differentiating under conditions known to promote neural differentiation. Retinal stem cells derived from human embryonic stem cells have highly similar properties to those directly isolated from the eye, and their progeny can similarly be driven to differentiate into photoreceptors. The findings presented in this thesis help to define intrinsic properties of adult neural and retinal precursors and provide a basis for manipulating these cells, potentially for future use in clinical applications.

Neural Development and Stem Cells

Neural Development and Stem Cells
Author: Mahendra S. Rao
Publisher: Springer Science & Business Media
Total Pages: 451
Release: 2007-10-28
Genre: Medical
ISBN: 1592599141

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Developing the second edition of Neural Development and Stem Cells was neces- tated by the rapid increase in our knowledge of the development of the nervous system. It has become increasingly clear that stem cells are a heterogeneous population that changes extensively during development. Perhaps the most important advance in our understanding of stem cell behavior has been the realization that regionalization of stem cells occurs early in development and this bias toward differentiation in phe- types of neurons or cells characteristic of a particular part of the brain appears to persist even after prolonged culture. We have therefore included additional chapters on olf- tory epithelial stem cells and retinal stem cells, both of which differ in their properties from ventricular zone and subventricular zone–derived neural stem cells. It is also now clear from an analysis of mutants and transgenics where the death or self-renewal pa- way is altered that cell death regulates stem cell number. As a consequence, this second edition includes a separate chapter on cell death that summarizes the important changes in the death pathway that occur as stem cells mature. The existing chapters in the book have also been extensively revised and updated by experts who have generously c- tributed their time and expertise. The chapters have been organized along the lines of our understanding of how the nervous system develops (Fig. 1, on p. vi).

Perspectives of Stem Cells

Perspectives of Stem Cells
Author: Henning Ulrich
Publisher: Springer Science & Business Media
Total Pages: 300
Release: 2010-01-14
Genre: Science
ISBN: 9048133750

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Stem cells are fascinating cell types. They can replicate themselves forever while retaining the potential to generate progeny with speci?c functions. Because of these special properties, stem cells have been subjects of intensive investigation, from understanding basic mechanisms underlying tissue generation, to modeling human diseases, to application for cell replacement therapy. Stem cells come in different forms. For example, mouse embryonic stem cells can general all cell types in a body, either in a dish or when put back into mouse embryos. On the other hand, neural stem cells in the adult brain generate neurons and glia cells that contribute to the brain’s plasticity. Rapid progress has been made in the stem cell ?eld with discov- ies published in a record speed. A quick Pubmed search has returned 2789 hits for “embryonic stem cells” and 815 hits for “adult neural stem cells/neurogenesis” in the year 2008 alone. It remains a taunting task for all who are interested in stem cells to keep up with rapidly accumulating literatures. The “Perspectives of Stem Cells” by a truly international team of experts provides a timely and invaluable highlight of the stem cell ?eld gearing toward future therapeutic applications in the nervous system. Stem cells with neural potentials have attracted a lot of attention because of their promise for cell replacement therapy, ranging from degenerative neurological dis- ders to spinal cord injuries.

Human Neural Stem Cells

Human Neural Stem Cells
Author: Leonora Buzanska
Publisher: Springer
Total Pages: 334
Release: 2018-09-12
Genre: Science
ISBN: 3319934856

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This book summarizes early pioneering achievements in the field of human neural stem cell (hNSC) research and combines them with the latest advances in stem cell technology, including reprogramming and gene editing. The powerful potential of hNSC to generate and repair the developing and adult CNS has been confirmed by numerous experimental in vitro and in vivo studies. The book presents methods for hNSC derivation and discusses the mechanisms underlying NSC in vitro fate decisions and their in vivo therapeutic mode of action. The long-standing dogma that the human central nervous system (CNS) lacks the ability to regenerate was refuted at the end of the 20th century, when evidence of the presence of neurogenic zones in the adult human brain was found. These neurogenic zones are home to human neural stem cells (hNSCs), which are capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. NSCs isolated from human CNS have a number of clinical advantages, especially the innate potential to differentiate into functional neural cells. Nevertheless, their full clinical exploitation has been hindered by limited access to the tissue and low expansion potential. The search for an alternative to CNS sources of autologous, therapeutically competent hNSCs was the driving force for the many studies proving the in vitro plasticity of different somatic stem cells to generate NSCs and their functional progeny. Now the era of induced pluripotent stem cells has opened entirely new opportunities to achieve research and therapeutic goals with the aid of hNSCs.

Neural Stem Cells

Neural Stem Cells
Author: Jane E. Bottenstein
Publisher: Springer Science & Business Media
Total Pages: 479
Release: 2007-05-08
Genre: Medical
ISBN: 0306483564

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Neural Stem Cells: Development and Transplantation provides comprehensive, critical and insightful reviews by leading experts in this exciting field of research. This volume will provide the latest data on neural stem cell properties and their therapeutic applications. This volume will be particularly useful for students, basic scientists, and clinicians in the academic or industrial sectors who have an interest in understanding neural development and its application to repairing the nervous system.

Characterisation of Neural Progenitors from the Adult Retina and Ciliary Epithelium

Characterisation of Neural Progenitors from the Adult Retina and Ciliary Epithelium
Author: I. Kokkinopoulos
Publisher:
Total Pages:
Release: 2009
Genre:
ISBN:

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The mammalian central neural retina (CNR) lacks the capability to regenerate, a phenomenon retained by lower vertebrates. However, retinal stem cells have been isolated from the ciliary epithelium of the mammalian retina. Chx10 is a paired-like homeobox transcription factor gene expressed in the presumptive neural retina of the invaginating optic vesicle. The Chx10 gene is expressed in the proliferating retinal progenitor cell population throughout retinal development hence is one of the earliest characterised RPC-specific markers. Mutations in the Chx10 homeobox gene cause reduced proliferation of retinal progenitor cells during development, leading to microphthalmia. Recently, it was showed that in the ocular retardation mouse model lacking Chx10 (Chx10orJ/orJ), dividing cells persist in the adult CNR, suggesting the existence of a dormant stem/progenitor population. The neurosphere-forming assay is a tool which has allowed scientists to study the behaviour of neural stem/progenitor cells in vitro. Here, I show that cells deriving from the CNR of the adult microphthalmic retina are proliferative and give rise to neurospheres in vitro, a characteristic of neural stem cells. However, these adult-derived CNR progenitors differ from those of the wildtype CE, leading to de-pigmented, larger and more numerous neurospheres expressing Müller glial cell markers. My results suggest that lack of Chx10 leads to maintenance of a dormant neural progenitor population in the adult CNR possible deriving from the abnormal appearance of GFAPpos Müller glia in late embryonic stages of the Chx10orJ/orJ retina. Furthermore, Chx10 is not required for in vitro proliferation of these progenitors. One of the cardinal features of stem cells is their differentiation potential and multipotency. My experiments illustrate that Chx10orJ/orJ CNR-derived neurospheres are able to differentiate in a similar fashion to wildtype CE-derived neurospheres. Furthermore, when neurospheres lacking Chx10 are placed in conditions that promote differentiation, they significantly up-regulate the expression of photoreceptor genes in comparison to wildtype. Hitherto, the developmental origin of CE-derived neurosphere-forming retinal stem cell is unclear. The ciliary body, where the CE is located in adult mammals, includes cells of mesodermal, neural crest and neural ectodermal origin. Here, data collected from lineage tracing analysis and in vivo BrdU-tagging experiments suggest that neurospheres are formed from BrdUpos cells observed in vivo, and that these cells originate from the embryonic anterior forebrain. The comparative analysis of the microphthalmic CNR retinal progenitors and CE-derived progenitors provides valuable information on cell properties relevant for potential cell-based replacement therapies, as well for retinal regeneration potential in mammals.

Neural Stem Cells for Brain and Spinal Cord Repair

Neural Stem Cells for Brain and Spinal Cord Repair
Author: Tanja Zigova
Publisher: Springer Science & Business Media
Total Pages: 438
Release: 2002-11-05
Genre: Medical
ISBN: 1592592988

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Active neuroscientists survey NSCs as potential tools for central nervous system and spinal cord repair by explaining their clinically significant fundamental properties, manipulations, and potential therapeutic paradigms. Their discussion of the fundamental biology of NSCs illustrates the signaling pathways that regulate stem cell division and differentiation, and defines the methods of NSC expansion and propagation, neuromorphogenesis, the factors determining cell fate both in vitro and in situ, and the induction of self-reparative processes within the brain. They also present strategies that may lead to fruitful clinical applications in the near future. These range from the replacement of degenerated, dysfunctional, or maldeveloped cells to the provision of factors that may protect, correct, recruit, promote self-repair, or mediate the connectivity of host cells.

Stem and Progenitor Cells in the Central Nervous System

Stem and Progenitor Cells in the Central Nervous System
Author: R.S. Nowakowski
Publisher: Karger Medical and Scientific Publishers
Total Pages: 212
Release: 2004
Genre: Medical
ISBN: 3805578709

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This publication focuses on the biology of stem and progenitor cells in the developing and mature central nervous system, their response to trauma and potential uses in therapy. The authors, who are leading experts in the field, address topical questions from both basic and clinical neuroscience perspectives such as: non-invasive imaging of stem cell division; the origins of regional diversity in cell types and cell numbers in the stem cell progeny; factors that regulate generation of neurons and glial cells from stem cells during normal development; the role of genetic and environmental factors in the regulation of stem cell function; the role of stem cells in mediating the effects of brain trauma and its recovery, and the therapeutic uses of stem cells. Offering a unique compilation of articles on the biology and the therapeutic applications of stem cells in the embryonic and mature nervous systems, this volume will be of great value to neuroscientists, developmental biologists, cancer biologists and clinical neurologists.

Neural Stem Cells

Neural Stem Cells
Author: Tanja Zigova
Publisher: Springer Science & Business Media
Total Pages: 373
Release: 2008-02-03
Genre: Medical
ISBN: 1592591868

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Over the last decade, neural stem cell research has provided penetrating insights into the plasticity and regenerative potential of the brain. Stem cells have been isolated from embryonic as well as adult central nervous system (CNS). Many non-CNS mammalian tissues also contain stem cells with a more limited repertoire: the replacement of tissue-specific cells throughout the li- time of the organism. Progress has been made in understanding fundamental stem cell properties that depend on the interplay of extrinsic signaling factors with intrinsic genetic programs within critical time frames. With this growing knowledge, scientists have been able to change a neural stem cell’s fate. - der certain conditions, neural stem cells have been induced to differentiate into cells outside the expected neural lineage and conversely, stem cells from nonneural tissue have been shown to transdifferentiate into cells with distinct neural phenotypes. At the moment, there is an accelerated effort to identify a readily ava- able, socially acceptable stem cell that can be induced to proliferate in an und- ferentiated state and that can be manipulated at will to generate diverse cells types. We are on the threshold of a great new therapeutic era of cellular therapy that has as great, if not greater, potential as the current pharmacologic era, g- rified by antibiotics, anesthetics, pain killers, immunosuppressants, and psyc- tropics.

Neural Stem Cells and Therapy

Neural Stem Cells and Therapy
Author: Tao Sun
Publisher: BoD – Books on Demand
Total Pages: 456
Release: 2012-02-15
Genre: Science
ISBN: 9533079584

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This book is a collective work of international experts in the neural stem cell field. The book incorporates the characterization of embryonic and adult neural stem cells in both invertebrates and vertebrates. It highlights the history and the most advanced discoveries in neural stem cells, and summarizes the mechanisms of neural stem cell development. In particular, this book provides strategies and discusses the challenges of utilizing neural stem cells for therapy of neurological disorders and brain and spinal cord injuries. It is suitable for general readers, students, doctors and researchers who are interested in understanding the principles of and new discoveries in neural stem cells and therapy.