Abstract
A number of factors more or less unique to multiple sclerosis have suggested that this disease may be particularly amenable to cell-based reparative therapies. The relatively focussed damage to oligodendrocytes and myelin at least in early disease implies that only a single population of cells need be replaced—and that the daunting problem of re-establishing connectivity does not apply. The presence of significant though partial spontaneous myelin repair in multiple sclerosis proves there to be no insurmountable barrier to remyelination intrinsic to the CNS: the therapeutic challenge becomes that of supplementing this spontaneous process, rather than creating repair de novo. Finally, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that future prospects for such therapies are not unrealistic. Nonetheless, particular and significant problems are not hard to list: the occurrence of innumerable lesions scattered throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory process, to name but a few. Here we review the progress and the areas where difficulties have yet to be resolved in efforts to develop remyelinating therapies for multiple sclerosis.
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Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Snyder EY (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851
Akiyama Y, Radtke C, Honmou O, Kocsis JD (2002) Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 39:229–236
Akiyama Y, Radtke C, Kocsis JD (2002) Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 22:6623–6630
Azizi SA, Stokes D, Augelli BJ, Digirolamo C, Prockop DJ (1998) Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats – similarities to astrocyte grafts. Proc Natl Acad Sci USA 95:3908–3913
Bachelin C, Lachapelle F, Girard C, Moissonnier P, Serguera-Lagache C, Mallet J, Fontaine D, Chojnowski A, Le GE, Nait-Oumesmar B, Baron-Van EA (2005) Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells. Brain 128:540–549
Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882
Barnett SC, Alexander CL, Iwashita Y, Gilson JM, Crowther J, Clark L, Dunn LT, Papanastassiou V, Kennedy PG, Franklin RJ (2000) Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons [see comments]. Brain 123:1581–1588
Barnett SC, Franklin RJM, Blakemore WF (1993) In vitro and in vivo analysis of a rat bipotential O-2A progenitor cell line containing the temperature-sensitive mutant gene of the SV40 large T antigen. Eur J Neurosci 5:1247–1260
Baron-Van Evercooren A, Avellana-Adalid V, Lachapelle F, Liblau R (1997) Schwann cell transplantation and myelin repair of the CNS. Mult Scler 3:157–161
Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Bruck W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123:1174–1183
Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901
Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 14:271–278
Bjorklund A (2000) Cell replacement strategies for neurodegenerative disorders. Novartis Found Symp 231:7–15; discussion 16–20
Blau HM (2002) A twist of fate. Nature 419:437
Braude P, Minger SL, Warwick RM (2005) Stem cell therapy: hope or hype? BMJ 330:1159–1160
Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779
Brierley CM, Crang AJ, Iwashita Y, Gilson JM, Scolding NJ, Compston DA, Blakemore WF (2001) Remyelination of demyelinated CNS axons by transplanted human schwann cells: the deleterious effect of contaminating fibroblasts. Cell Transplant 10:305–315
Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, Duncan ID, McKay RD (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285:754–756
Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA (1999) Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci USA 96:15256–15261
Cao Q, Benton RL, Whittemore SR (2002) Stem cell repair of central nervous system injury. J Neurosci Res 68:501–510
Carroll WM, Jennings AR (1994) Early recruitment of oligodendrocyte precursors in CNS demyelination. Brain 117:563–578
Chang A, Nishiyama A, Peterson J, Prineas J, Trapp BD (2000) NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 20:6404–6412
Charles P, Hernandez MP, Stankoff B, Aigrot MS, Colin C, Rougon G, Zalc B, Lubetzki C (2000) Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule. Proc Natl Acad Sci USA 97:7585–7590
Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011
Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurology 1:92–99
Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, Lu M, Rosenblum M (2000) Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 11:3001–3005
Clarke D, Frisen J (2001) Differentiation potential of adult stem cells. Curr Opin Genet Dev 11:575–580
Cogle CR, Yachnis AT, Laywell ED, Zander DS, Wingard JR, Steindler DA, Scott EW (2004) Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet 363:1432–1437
Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 98:7841–7845
Compston DAS (1996) Remyelination of the central nervous system. Mult Scler 1:388–392
Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438
Crain BJ, Tran SD, Mezey E (2005) Transplanted human bone marrow cells generate new brain cells. J Neurol Sci 233:121–123
Cuzner ML, Loughlin AJ, Mosley K, Woodroofe MN (1994) The role of microglia macrophages in the processes of inflammatory demyelination and remyelination. Neuropathol Appl Neurobiol 20:200–201
Davie CA, Barker GJ, Webb S, Tofts PS, Thompson AJ, Harding AE, McDonald WI, Miller DH (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118:1583–1592
De Stefano N, Matthews PM, Antel JP, Preul M, Francis G, Arnold DL (1995) Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol 38:901–909
Deloire-Grassin MS, Brochet B, Quesson B, Delalande C, Dousset V, Canioni P, Petry KG (2000) In vivo evaluation of remyelination in rat brain by magnetization transfer imaging. J Neurol Sci 178:10–16
Deng W, Obrocka M, Fischer I, Prockop DJ (2001) In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 282:148–152
Devine SM, Cobbs C, Jennings M, Batholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into non-human primates. Blood 101:2999–3001
Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54
Duncan ID, Grever WE, Zhang SC (1997) Repair of myelin disease: strategies and progress in animal models. Mol Med Today 3:554–561
Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49:377–391
Franklin RJ, Barnett SC (2000) Olfactory ensheathing cells and CNS regeneration: the sweet smell of success? Neuron 28:15–18
Franklin RJ, Blaschuk KL, Bearchell MC, Prestoz LL, Setzu A, Brindle KM, Ffrench-Constant C (1999) Magnetic resonance imaging of transplanted oligodendrocyte precursors in the rat brain. Neuroreport 10:3961–3965
Franklin RJM, Bayley SA, Blakemore WF (1996) Transplanted CG4 cells (an oligodendrocyte progenitor cell line) survive, migrate, and contribute to repair of areas of demyelination in X-irradiated and damaged spinal cord but not in normal spinal cord. Exp Neurol 137:263–276
Franklin RJM, Blakemore WF (1993) Requirements for Schwann cell migration within CNS environments: A viewpoint. Int J Dev Neurosci 11:641–649
Franklin RJM, Gilson JM, Franceschini IA, Barnett SC (1996) Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell-line into areas of demyelination in the adult CNS. Glia 17:217–224
Griffiths I, Klugmann M, Anderson T, Yool D, Thomson C, Schwab MH, Schneider A, Zimmermann F, McCulloch M, Nadon N, Nave KA (1998) Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280:1610–1613
Groves AK, Barnett SC, Franklin RJM, Crang AJ, Mayer M, Blakemore WF, Noble M (1993) Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362:453–455
Harrison B (1985) Schwann cell and oligodendrocyte remyelination in lysolecithin-induced lesions in irradiated rat spinal cord. J Neurol Sci 67:143–159
Harrison BM (1980) Remyelination by cells introduced into a stable demyelinating lesion in the central nervous system. J Neurol Sci 46:63–81
Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A (2001) The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure. Brain 124:962–973
Honmou O, Felts PA, Waxman SG, Kocsis JD (1996) Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J Neurosci 16:3199–3208
Ianus A, Holz GG, Theise ND, Hussain MA (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111:843–850
Imaizumi T, Lankford KL, Waxman SG, Greer CA, Kocsis JD (1998) Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. J Neurosci 18:6176–6185
Itoyama Y, Webster HD, Richardson EP Jr, Trapp BD (1983) Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions. Ann Neurol 14:339–346
Jeffery ND, Crang AJ, O’leary MT, Hodge SJ, Blakemore WF (1999) Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord. Eur J Neurosci 11:1508–1514
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49
Kato T, Honmou O, Uede T, Hashi K, Kocsis JD (2000) Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia 30:209–218
Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705
Kim BJ, Seo JH, Bubien JK, Young SO (2002) Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro. Neuroreport 13:1185–1188
Koc ON, Lazarus HM (2001) Mesenchymal stem cells: heading into the clinic. Bone Marrow Transplant 27:235–239
Kohama I, Lankford KL, Preiningerova J, White FA, Vollmer TL, Kocsis JD (2001) Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord. J Neurosci 21:944–950
Korbling M, Estrov Z (2003) Adult stem cells for tissue repair. N Engl J Med 349:570–582
Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 157:267–276
Kotter MR, Li WW, Zhao C, Franklin RJ (2006) Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci 26:328–332
Krause DS (2002) Plasticity of marrow-derived stem cells. Gene Ther 9:754–758
Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377
Kukekov VG, Laywell ED, Suslov O, Davies K, Scheffler B, Thomas LB, O’Brien TF, Kusakabe M, Steindler DA (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain. Exp Neurol 156:333–344
Lakatos A, Franklin RJ, Barnett SC (2000) Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 32:214–225
Langford LA, Porter S, Bunge RP (1988) Immortalized rat Schwann cells produce tumours in vivo. J Neurocytol 17:521–529
Lassmann H, Bruck W, Lucchinetti CF, Rodriguez M (1997) Remyelination in multiple sclerosis. Mult Scler 3:133–136
Lavdas A, Franceschini I, Dubois-Dalcq M, Matsas R (2006) Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro. Glia in press
Leocani L, Medaglini S, Comi G (2000) Evoked potentials in monitoring multiple sclerosis. Neurol Sci 21:S889–S891
Lescaudron L, Unni D, Dunbar GL (2003) Autologous adult bone marrow stem cell transplantation in an animal model of Huntington’s disease: behavioral and morphological outcomes. Int J Neurosci 113:945–956
Levi ADO, Bunge RP (1994) Studies of myelin formation after transplantation of human SchwannX X cells into the severe combined immunodeficient mouse. Exp Neurol 130:41–52
Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414
Li Y, Chen J, Wang L, Zhang L, Lu M, Chopp M (2001) Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neurosci Lett 316:67–70
Lipton SA (1986) Blockade of electrical-activity promotes the death of mammalian retinal ganglion-cells in culture. Proc Natl Acad Sci USA 83:9774–9778
Ludwin S (1988) Remyelination in the central nervous system and in the peripheral nervous system. Adv Neurol 47:215–254
Maeda Y, Solanky M, Menonna J, Chapin J, Li W, Dowling P (2001) Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions. Ann Neurol 49:776–785
Masuya M, Drake CJ, Fleming PA, Reilly CM, Zeng H, Hill WD, Martin-Studdard A, Hess DC, Ogawa M (2003) Hematopoietic origin of glomerular mesangial cells. Blood 101:2215–2218
Mazzini L, Fagioli F, Boccaletti R, Mareschi K, Oliveri G, Olivieri C, Pastore I, Marasso R, Madon E (2003) Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans. Amyotrophic lateral sclerosis and other motor neuron disorders: official publication of the world federation of neurology, Research group on motor neuron diseases 4:158–161
Medvinsky A, Smith A (2003) Stem cells: fusion brings down barriers. Nature 422:823–825
Merkler D, Boretius S, Stadelmann C, Ernsting T, Michaelis T, Frahm J, Bruck W (2005) Multicontrast MRI of remyelination in the central nervous system. NMR Biomed 23:7710–7718
MeyerFranke A, Kaplan MR, Pfrieger FW, Barres BA (1995) Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture. Neuron 15:805–819
Mezey E, Chandross KJ (2000) Bone marrow: a possible alternative source of cells in the adult nervous system. Eur J Pharmacol 405:297–302
Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782
Morrissey TK, Levi AD, Nuijens A, Sliwkowski MX, Bunge RP (1995) Axon-induced mitogenesis of human Schwann cells involves heregulin and p185erbB2. Proc Natl Acad Sci USA 92:1431–1435
Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS (2005) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396
Ogata J, Feigin I (1975) Schwann cells and regenerated peripheral myelin in multiple sclerosis: an ultrastructural study. Neurology 25:713–716
Park KI, Ourednik J, Ourednik V, Taylor RM, Aboody KS, Auguste KI, Lachyankar MB, Redmond DE, Snyder EY (2002) Global gene and cell replacement strategies via stem cells. Gene Ther 9:613–624
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422:688–694
Poulsom R, Alison MR, Forbes SJ, Wright NA (2002) Adult stem cell plasticity. J Pathol 197:441–456
Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137–151
Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5:22–31
Prineas JW, Kwon EE, Goldenberg PZ (1989) Multiple sclerosis: oligodendrocyte proliferation and differentiation in fresh lesions. Lab Inv 61:489–503
Prockop DJ (2002) Adult stem cells gradually come of age. Nat Biotechnol 20:791–792
Raine CS, Cross AH (1989) Axonal dystrophy as a consequence of long-term demyelination. Lab Invest 60:714–725
Raine CS, Scheinberg L, Waltz JM (1981) Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion. Lab Invest 45:534–546
Raine CS, Wu E (1993) Multiple sclerosis: remyelination in acute lesions. J Neuropathol Exp Neurol 52:199–204
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaille CM (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98:2615–2625
Rice CM, Halfpenny C, Scolding NJ (2004) Cell therapy in demyelinating diseases. NeuroRx 1:415–423
Rice CM, Scolding NJ (2004) Adult stem cells – reprogramming neurological repair? Lancet 364:193–199
Rogister B, Ben Hur T, Dubois-Dalcq M (1999) From neural stem cells to myelinating oligodendrocytes. Mol Cell Neurosci 14:287–300
Roy NS, Wang S, Harrison-Restelli C, Benraiss A, Fraser RA, Gravel M, Braun PE, Goldman SA (1999) Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. J Neurosci 19:9986–9995
Rutkowski JL, Kirk CJ, Lerner MA, Tennekoon GI (1995) Purification and expansion of human schwann cells in vitro. Nat Med 1:80–83
Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256
Sasaki M, Honmou O, Akiyama Y, Uede T, Hashi K, Kocsis JD (2001) Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 35:26–34
Scolding N (2001) New cells from old. Lancet 357:329–330
Scolding N (2005) Stem-cell therapy: hope and hype. Lancet 365:2073–2075
Scolding N, Franklin R (1998) Axon loss in multiple sclerosis. Lancet 352:340–341
Scolding NJ, Franklin RJM (1999) Remyelination in demyelinating disease. Clin Neurol Int Pract Res 6:525–548
Scolding NJ, Franklin RJM, Stevens S, Heldin CH, Compston DAS, Newcombe J (1998) Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 121:2221–2228
Smith KJ, McDonald WI (1999) The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc Lond B Biol Sci 354:1649–1673
Smith PM, Franklin RJ (2001) The effect of immunosuppressive protocols on spontaneous CNS remyelination following toxin-induced demyelination. J Neuroimmunol 119:261–268
Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17:1429–1436
Song SK, Yoshino J, Le TQ, Lin SJ, Sun SW, Cross AH, Armstrong RC (2005) Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 26:132–140
Targett MP, Sussman J, Scolding N, OLeary MT, Compston DAS, Blakemore WF (1996) Failure to achieve remyelination of demyelinated rat axons following transplantation of glial cells obtained from the adult human brain. Neuropath App Neurobiol 22:199–206
Tontsch U, Archer DR, Dubois-Dalcq M, Duncan ID (1994) Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc Natl Acad Sci USA 91:11616–11620
Tran SD, Pillemer SR, Dutra A, Barrett AJ, Brownstein MJ, Key S, Pak E, Leakan RA, Kingman A, Yamada KM, Baum BJ, Mezey E (2003) Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study. Lancet 361:1084–1088
Utzschneider DA, Archer DR, Kocsis JD, Waxman SG, Duncan ID (1994) Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proc Natl Acad Sci USA 91:53–57
Vassilopoulos G, Wang PR, Russell DW (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901–904
Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422:897–901
Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci USA 100:2088–2093
Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, Reynolds BA (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 16:7599–7609
Weissman IL (2000) Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287:1442–1446
Wilkins A, Majed H, Layfield R, Compston A, Chandran S (2003) Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factor. J Neurosci 23:4967–4974
Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann G, Roy NS, Goldman SA (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 10:93–97
Wolswijk G (2000) Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis. Brain 123(Pt 1):105–115
Wolswijk G (1998) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci 18:601–609
Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370
Woodruff RH, Franklin RJ (1999) Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study. Glia 25:216–228
Zhang SC, Ge B, Duncan ID (1999) Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc Natl Acad Sci USA 96:4089–4094
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The authors thank the UK Multiple Sclerosis Society and the Ipsen Trust for support. The Burden Chair Clinical Neurosciences is supported by the Burden Trust.
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Rice, C., Scolding, N. Strategies for achieving and monitoring myelin repair. J Neurol 254, 275–283 (2007). https://doi.org/10.1007/s00415-006-0455-x
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DOI: https://doi.org/10.1007/s00415-006-0455-x