Cellular and genetic characterization of human adult bone marrow-derived neural stem-like cells: a potential antiglioma cellular vector.

We describe the in vitro isolation and expansion of cells capable of forming neurosphere-like aggregates from human adult bone marrow. Cells within these passaged spheroids can differentiate into astrocytes, specific neuronal subtypes, and oligodendrocytes and have gene expression profiles similar to human fetal brain-derived neural stem cells. Genetically modified neural-competent bone marrow-derived cells efficiently migrate toward distant sites of brain injury and tumor in vivo, where they differentiate and express therapeutic transgenes when transplanted into the brains of mice. These studies suggest that adult bone marrow may serve as a large reservoir for autologous neural stem-like cells for future therapeutic strategies.

[1]  Fred H. Gage,et al.  Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo , 2003, Nature Neuroscience.

[2]  K. Black,et al.  Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. , 2002, Cancer research.

[3]  John T. Dimos,et al.  A Stem Cell Molecular Signature , 2002, Science.

[4]  D. Melton,et al.  "Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells , 2002, Science.

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

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

[7]  Stuart H. Orkin,et al.  Hematopoiesis and stem cells: plasticity versus developmental heterogeneity , 2002, Nature Immunology.

[8]  H. Fine,et al.  Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector. , 2002, Neoplasia.

[9]  Marius Wernig,et al.  In vitro differentiation of transplantable neural precursors from human embryonic stem cells , 2001, Nature Biotechnology.

[10]  C. Verfaillie,et al.  Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. , 2001, Blood.

[11]  C. Svendsen,et al.  Neurons from stem cells: preventing an identity crisis , 2001, Nature Reviews Neuroscience.

[12]  Peter J. Donovan,et al.  The end of the beginning for pluripotent stem cells , 2001, Nature.

[13]  Sally Temple,et al.  The development of neural stem cells , 2001, Nature.

[14]  A. Sadikot,et al.  Isolation of multipotent adult stem cells from the dermis of mammalian skin , 2001, Nature Cell Biology.

[15]  D. Geschwind,et al.  From hematopoiesis to neuropoiesis: Evidence of overlapping genetic programs , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. DePinho,et al.  Malignant glioma: genetics and biology of a grave matter. , 2001, Genes & development.

[17]  Neil D. Theise,et al.  Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell , 2001, Cell.

[18]  I. Pollack,et al.  Direct stimulation of apoptotic signaling by soluble Apo2l/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  David M. Bodine,et al.  Bone marrow cells regenerate infarcted myocardium , 2001, Nature.

[20]  Fred H. Gage,et al.  Can stem cells cross lineage boundaries? , 2001, Nature Medicine.

[21]  Janet Rossant,et al.  Direct Neural Fate Specification from Embryonic Stem Cells A Primitive Mammalian Neural Stem Cell Stage Acquired through a Default Mechanism , 2001, Neuron.

[22]  D. Baker,et al.  Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation , 2001, Nature Immunology.

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

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

[25]  P. Black,et al.  Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Xin Wang,et al.  Purified hematopoietic stem cells can differentiate into hepatocytes in vivo , 2000, Nature Medicine.

[27]  M. Raff,et al.  Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. , 2000, Science.

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

[29]  N. Sampas,et al.  Molecular classification of cutaneous malignant melanoma by gene expression profiling , 2000, Nature.

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

[31]  E. Jauniaux,et al.  Human Neural Precursor Cells Express Low Levels of Telomerase in Vitro and Show Diminishing Cell Proliferation with Extensive Axonal Outgrowth following Transplantation , 2000, Experimental Neurology.

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

[33]  R. McKay,et al.  Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells , 2000, Nature Biotechnology.

[34]  G. Finocchiaro,et al.  Gene therapy of experimental brain tumors using neural progenitor cells , 2000, Nature Medicine.

[35]  I. Weissman,et al.  Translating stem and progenitor cell biology to the clinic: barriers and opportunities. , 2000, Science.

[36]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

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

[38]  Michael Bittner,et al.  Data analysis and integration: of steps and arrows , 1999, Nature Genetics.

[39]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

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

[41]  M. Bittner,et al.  Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. , 1998, Cancer research.

[42]  R. Sidman,et al.  Engraftable human neural stem cells respond to development cues, replace neurons, and express foreign genes , 1998, Nature Biotechnology.

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

[44]  S. K. Malhotra,et al.  Reactive astrocytes: cellular and molecular cues to biological function , 1997, Trends in Neurosciences.

[45]  R. Weinberg,et al.  hEST2, the Putative Human Telomerase Catalytic Subunit Gene, Is Up-Regulated in Tumor Cells and during Immortalization , 1997, Cell.

[46]  P. Wen,et al.  Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth , 1997, Nature Medicine.

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

[48]  J. Gentle,et al.  Randomization and Monte Carlo Methods in Biology. , 1990 .

[49]  R. McKay,et al.  CNS stem cells express a new class of intermediate filament protein , 1990, Cell.