Neural Stem Cells: An Overview

Abstract— This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.

[1]  J. R. Coleman,et al.  Extinction of muscle-specific properties in somatic cell heterokaryons. , 1984, Developmental biology.

[2]  M. Loeffler,et al.  Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. , 1990, Development.

[3]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[4]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[5]  Angelo L. Vescovi,et al.  bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells , 1993, Neuron.

[6]  T. Kilpatrick,et al.  Cloning and growth of multipotential neural precursors: Requirements for proliferation and differentiation , 1993, Neuron.

[7]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[8]  Brent A. Reynolds,et al.  Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells , 1994, Neuron.

[9]  F. Gage,et al.  Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  I. Weissman,et al.  The biology of hematopoietic stem cells. , 1995, Annual review of cell and developmental biology.

[11]  D. Williams,et al.  Matrix molecule interactions with hematopoietic stem cells. , 1995, Experimental hematology.

[12]  F. Gage,et al.  FGF-2-Responsive Neuronal Progenitors Reside in Proliferative and Quiescent Regions of the Adult Rodent Brain , 1995, Molecular and Cellular Neuroscience.

[13]  S. Weiss,et al.  Is there a neural stem cell in the mammalian forebrain? , 1996, Trends in Neurosciences.

[14]  Brent A. Reynolds,et al.  Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis , 1996, The Journal of Neuroscience.

[15]  S. Weiss,et al.  Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. , 1996, Developmental biology.

[16]  H. Cameron,et al.  Regulation of neuronal birth, migration and death in the rat dentate gyrus. , 1996, Developmental neuroscience.

[17]  E. Parati,et al.  Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  D. van der Kooy,et al.  In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  C. Sotelo,et al.  Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation. , 1996, The Journal of comparative neurology.

[20]  D. Steindler,et al.  The subependymal zone: "brain marrow". , 1996, Progress in brain research.

[21]  Arturo Alvarez-Buylla,et al.  Chain Migration of Neuronal Precursors , 1996, Science.

[22]  Hynek Wichterle,et al.  Direct Evidence for Homotypic, Glia-Independent Neuronal Migration , 1997, Neuron.

[23]  A. Fasolo,et al.  Glial Tubes in the Rostral Migratory Stream of the Adult Rat , 1997, Brain Research Bulletin.

[24]  I. Weissman,et al.  Hematopoietic stem cells: challenges to expectations. , 1997, Current opinion in immunology.

[25]  D. van der Kooy,et al.  Transforming Growth Factor-α Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma , 1997, The Journal of Neuroscience.

[26]  F. Gage,et al.  Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain , 1997, The Journal of Neuroscience.

[27]  David J. Anderson,et al.  Regulatory Mechanisms in Stem Cell Biology , 1997, Cell.

[28]  F. Gage,et al.  Stem cells of the central nervous system. , 1998, Current opinion in neurobiology.

[29]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[30]  D. van der Kooy,et al.  CNS stem cells: where's the biology (a.k.a. beef)? , 1998, Journal of neurobiology.

[31]  E. Parati,et al.  Isolation and intracerebral grafting of nontransformed multipotential embryonic human CNS stem cells. , 1999, Journal of neurotrauma.

[32]  M. Carpenter,et al.  In Vitro Expansion of a Multipotent Population of Human Neural Progenitor Cells , 1999, Experimental Neurology.

[33]  M. Baslow The existence of molecular water pumps in the nervous system: a review of the evidence , 1999, Neurochemistry International.

[34]  E. Parati,et al.  Isolation and Cloning of Multipotential Stem Cells from the Embryonic Human CNS and Establishment of Transplantable Human Neural Stem Cell Lines by Epigenetic Stimulation , 1999, Experimental Neurology.

[35]  C. Gross,et al.  Neurogenesis in the neocortex of adult primates. , 1999, Science.

[36]  D. Kooy,et al.  Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain , 1999, Neuroscience.

[37]  A. Fasolo,et al.  Carnosine-related dipeptides in the mammalian brain , 1999, Progress in Neurobiology.

[38]  E. Snyder,et al.  Establishment and Properties of Neural Stem Cell Clones: Plasticity In Vitro and In Vivo , 1999, Brain pathology.

[39]  N. Honda,et al.  Mouse C2 myoblast cells resist HVJ (Sendai virus)-mediated cell fusion in the proliferating stage but become capable of fusion after differentiation. , 1999, Differentiation; research in biological diversity.

[40]  A. Vescovi,et al.  Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. , 1999, Science.

[41]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[42]  A. Fasolo,et al.  The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain , 1999, Brain Research Bulletin.

[43]  E. Parati,et al.  Epidermal and Fibroblast Growth Factors Behave as Mitogenic Regulators for a Single Multipotent Stem Cell-Like Population from the Subventricular Region of the Adult Mouse Forebrain , 1999, The Journal of Neuroscience.

[44]  Daniel A. Lim,et al.  Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain , 1999, Cell.

[45]  D. Steindler,et al.  Marrow-mindedness: a perspective on neuropoiesis , 1999, Trends in Neurosciences.

[46]  T. Palmer,et al.  Fibroblast Growth Factor-2 Activates a Latent Neurogenic Program in Neural Stem Cells from Diverse Regions of the Adult CNS , 1999, The Journal of Neuroscience.

[47]  M. Goodell,et al.  Hematopoietic potential of stem cells isolated from murine skeletal muscle. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Jonas Frisén,et al.  Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System , 1999, Cell.

[49]  D J Prockop,et al.  Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[50]  I. Black,et al.  Adult rat and human bone marrow stromal cells differentiate into neurons , 2000, Journal of neuroscience research.

[51]  W. Janssen,et al.  Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro , 2000, Experimental Neurology.

[52]  S. Mckercher,et al.  Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. , 2000, Science.

[53]  K. Chandross,et al.  Bone marrow: a possible alternative source of cells in the adult nervous system. , 2000, European journal of pharmacology.

[54]  J. García-Verdugo,et al.  Noggin Antagonizes BMP Signaling to Create a Niche for Adult Neurogenesis , 2000, Neuron.

[55]  Blair R. Leavitt,et al.  Induction of neurogenesis in the neocortex of adult mice , 2000, Nature.

[56]  I. Weissman,et al.  Direct isolation of human central nervous system stem cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[57]  H. Blau,et al.  From marrow to brain: expression of neuronal phenotypes in adult mice. , 2000, Science.

[58]  D. van der Kooy,et al.  Retinal stem cells in the adult mammalian eye. , 2000, Science.

[59]  Giulio Cossu,et al.  Skeletal myogenic potential of human and mouse neural stem cells , 2000, Nature Neuroscience.

[60]  J. Kleinman,et al.  Localization of epidermal growth factor receptors and putative neuroblasts in human subependymal zone , 2000, The Journal of comparative neurology.

[61]  Elizabeth Gould,et al.  Regulation of hippocampal neurogenesis in adulthood , 2000, Biological Psychiatry.

[62]  U. Lendahl,et al.  Generalized potential of adult neural stem cells. , 2000, Science.

[63]  M. C. Hu,et al.  Identification of a candidate human neurohematopoietic stem-cell population. , 2001, Blood.

[64]  J. García-Verdugo,et al.  Astrocytes Give Rise to New Neurons in the Adult Mammalian Hippocampus , 2001, The Journal of Neuroscience.

[65]  T. Weissman,et al.  Neurons derived from radial glial cells establish radial units in neocortex , 2001, Nature.

[66]  Federica Limana,et al.  Mobilized bone marrow cells repair the infarcted heart, improving function and survival , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Arturo Alvarez-Buylla,et al.  A unified hypothesis on the lineage of neural stem cells , 2001, Nature Reviews Neuroscience.

[68]  G. Corfas,et al.  Extracellular Signals That Regulate the Tangential Migration of Olfactory Bulb Neuronal Precursors: Inducers, Inhibitors, and Repellents , 2001, The Journal of Neuroscience.

[69]  Perry F. Bartlett,et al.  Purification of a pluripotent neural stem cell from the adult mouse brain , 2001, Nature.

[70]  M. Rudnicki,et al.  Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. , 2001, Differentiation; research in biological diversity.

[71]  E. Hirayama,et al.  CHARACTERISATION OF MYOGENIC CELL MEMBRANE: II. DYNAMIC CHANGES IN MEMBRANE LIPIDS DURING THE DIFFERENTIATION OF MOUSE C2 MYOBLAST CELLS , 2001, Cell biology international.

[72]  C. Gross,et al.  Adult-generated hippocampal and neocortical neurons in macaques have a transient existence , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[73]  M. Luskin,et al.  Neurogenesis in the Subventricular Zone and Rostral Migratory Stream of the Neonatal and Adult Primate Forebrain , 2001, Experimental Neurology.

[74]  R. Galli,et al.  Cultures of Stem Cells of the Central Nervous System , 2001 .

[75]  P. Rakic,et al.  Cell Proliferation Without Neurogenesis in Adult Primate Neocortex , 2001, Science.

[76]  C. Robertson,et al.  Failure of bone marrow cells to transdifferentiate into neural cells in vivo. , 2002, Science.

[77]  E. Tanaka,et al.  Ectoderm to Mesoderm Lineage Switching During Axolotl Tail Regeneration , 2002, Science.

[78]  I. Weissman,et al.  Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells , 2002, Science.

[79]  Arturo Alvarez-Buylla,et al.  EGF Converts Transit-Amplifying Neurogenic Precursors in the Adult Brain into Multipotent Stem Cells , 2002, Neuron.

[80]  D. Kooy,et al.  Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations , 2002, Nature Medicine.

[81]  R. Galli,et al.  Emx2 regulates the proliferation of stem cells of the adult mammalian central nervous system. , 2002, Development.

[82]  S. McKinney-Freeman,et al.  Muscle-derived hematopoietic stem cells are hematopoietic in origin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[83]  R. McKay A more astonishing hypothesis , 2002, Nature Biotechnology.

[84]  M. Grompe,et al.  Kinetics of liver repopulation after bone marrow transplantation. , 2002, The American journal of pathology.

[85]  T. Papayannopoulou,et al.  Cells with hemopoietic potential residing in muscle are itinerant bone marrow-derived cells. , 2002, Experimental hematology.

[86]  Arturo Alvarez-Buylla,et al.  Neurogenesis in Adult Subventricular Zone , 2002, The Journal of Neuroscience.

[87]  P. Weiss,et al.  Primate skeletal muscle contains cells capable of sustaining in vitro hematopoiesis. , 2002, Experimental hematology.

[88]  K. E. Jay,et al.  Emergence of muscle and neural hematopoiesis in humans. , 2002, Blood.

[89]  A. Vescovi,et al.  Hematopoietic potential of neural stem cells , 2002, Nature Medicine.

[90]  E. Scott,et al.  Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion , 2002, Nature.

[91]  R. Coggeshall,et al.  Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat , 2002, Nature Neuroscience.

[92]  R. Galli,et al.  Adult neural stem cells: plasticity and developmental potential , 2002, Journal of Physiology-Paris.

[93]  S. Temple,et al.  LeX/ssea-1 Is Expressed by Adult Mouse CNS Stem Cells, Identifying Them as Nonependymal , 2002, Neuron.

[94]  A. Álvarez-Buylla,et al.  Multipotent Neural Stem Cells Reside into the Rostral Extension and Olfactory Bulb of Adult Rodents , 2002, The Journal of Neuroscience.

[95]  M. Valk,et al.  Transplanted bone marrow generates new neurons in human brains , 2003 .

[96]  Mark Denham,et al.  Stem Cells: An Overview , 2005, Current protocols in cell biology.

[97]  B. Wang,et al.  Changing potency by spontaneous fusion , 2022 .