Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons

The potential of bone marrow cells to differentiate into myelin‐forming cells and to repair the demyelinated rat spinal cord in vivo was studied using cell transplantation techniques. The dorsal funiculus of the spinal cord was demyelinated by x‐irradiation treatment, followed by microinjection of ethidium bromide. Suspensions of a bone marrow cell fraction acutely isolated from femoral bones in LacZ transgenic mice were prepared by centrifugation on a density gradient (Ficoll‐Paque) to remove erythrocytes, platelets, and debris. The isolated cell fraction contained hematopoietic and nonhematopoietic stem and precursor cells and lymphocytes. The cells were transplanted into the demyelinated dorsal column lesions of immunosuppressed rats. An intense blue β‐galactosidase reaction was observed in the transplantation zone. The genetically labeled bone marrow cells remyelinated the spinal cord with predominately a peripheral pattern of myelination reminiscent of Schwann cell myelination. Transplantation of CD34+ hematopoietic stem cells survived in the lesion, but did not form myelin. These results indicate that bone marrow cells can differentiate in vivo into myelin‐forming cells and repair demyelinated CNS. GLIA 35:26–34, 2001. © 2001 Wiley‐Liss, Inc.

[1]  J. Kocsis,et al.  Transplantation of Clonal Neural Precursor Cells Derived from Adult Human Brain Establishes Functional Peripheral Myelin in the Rat Spinal Cord , 2001, Experimental Neurology.

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

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

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

[5]  J. Kocsis,et al.  Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord , 2000, Glia.

[6]  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.

[7]  T. Ben-Hur,et al.  Polysialylated Neural Cell Adhesion Molecule-Positive CNS Precursors Generate Both Oligodendrocytes and Schwann Cells to Remyelinate the CNS after Transplantation , 1999, The Journal of Neuroscience.

[8]  R. McKay,et al.  Embryonic stem cell-derived glial precursors: a source of myelinating transplants. , 1999, Science.

[9]  E. Snyder,et al.  "Global" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Dawson,et al.  Targeting of marrow-derived astrocytes to the ischemic brain. , 1999, Neuroreport.

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

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

[13]  S. Waxman,et al.  Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord , 1998, The Journal of Neuroscience.

[14]  D. Prockop,et al.  Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats--similarities to astrocyte grafts. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Dunnett,et al.  Long-Term Survival of Human Central Nervous System Progenitor Cells Transplanted into a Rat Model of Parkinson's Disease , 1997, Experimental Neurology.

[16]  J. D. Macklis,et al.  Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  I. Duncan,et al.  Myelination Following Transplantation of EGF-Responsive Neural Stem Cells into a Myelin-Deficient Environment , 1997, Experimental Neurology.

[18]  C. Hulsebosch,et al.  Culture, expansion, and transplantation of human fetal neural progenitor cells. , 1997, Transplantation proceedings.

[19]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[20]  T. Priestley,et al.  In vitro propagation and inducible differentiation of multipotential progenitor cells from human fetal brain , 1997, Neuroscience.

[21]  R. Franklin,et al.  Schwann cell‐like myelination following transplantation of an olfactory bulb‐ensheathing cell line into areas of demyelination in the adult CNS , 1996, Glia.

[22]  S. Waxman,et al.  Restoration of Normal Conduction Properties in Demyelinated Spinal Cord Axons in the Adult Rat by Transplantation of Exogenous Schwann Cells , 1996, The Journal of Neuroscience.

[23]  A. Björklund,et al.  Host regulation of glial markers in intrastriatal grafts of conditionally immortalized neural stem cell lines , 1996, Neuroreport.

[24]  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.

[25]  Martin Rydmark,et al.  Morphology of normal peripheral axons , 1995 .

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

[27]  I. Duncan,et al.  Myelination by Cryopreserved Xenografts and Allografts in the Myelin-Deficient Rat , 1994, Experimental Neurology.

[28]  S. Waxman,et al.  Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[29]  C. Lois,et al.  Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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

[31]  A. Crang,et al.  The use of cultured autologous Schwann cells to remyelinate areas of persistent demyelination in the central nervous system , 1985, Journal of the Neurological Sciences.

[32]  W. Blakemore Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve , 1977, Nature.

[33]  A. Crang,et al.  Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system. , 1988, Developmental neuroscience.

[34]  P I Terasaki,et al.  Long-term survival. , 1988, Clinical transplants.