Skip to main content

Advertisement

SpringerLink
Log in

Myelin Restoration: Progress and Prospects for Human Cell Replacement Therapies

  • REVIEW
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Oligodendrocytes are the primary source of myelin in the adult central nervous system (CNS), and their dysfunction or loss underlies several diseases of both children and adults. Dysmyelinating and demyelinating diseases are thus attractive targets for cell-based strategies since replacement of a single presumably homogeneous cell type has the potential to restore functional levels of myelin. To understand the obstacles that cell-replacement therapy might face, we review oligodendrocyte biology and emphasize aspects of oligodendrocyte development that will need to be recapitulated by exogenously transplanted cells, including migration from the site of transplantation, axon recognition, terminal differentiation, axon wrapping, and myelin production and maintenance. We summarize studies in which different types of myelin-forming cells have been transplanted into the CNS and highlight the continuing challenges regarding the use of cell-based therapies for human white matter disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ATP:

Adenosine triphosphate

CNP:

2′,3′-Cyclic nucleotide-3′phosphodiesterase

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

EAE:

Experimental autoimmune encephalomyelitis

GalC:

Galactocerebrosidase

IGF-1:

Insulin-like growth factor 1

iPSCs:

Induced pluripotent stem cells

miRs:

MicroRNAs

MAG:

Myelin-associated glycoprotein

MBP:

Myelin basic protein

MOG:

Myelin/oligodendrocyte glycoprotein

MS:

Multiple sclerosis

MSC:

Mesenchymal stem cells

mTOR:

Mammalian target of rapamycin

NSCs:

Neural stem cells

O2A:

Oligodendrocyte-type 2 astrocyte precursor

OPCs:

Oligodendrocyte precursors

PDGFR:

Platelet derived growth factor receptor

Plp:

Proteolipid protein

PMD:

Pelizaeus–Merzbacher disease

PNS:

Peripheral nervous system

PTEN:

Phosphatase and tensin homolog

T3:

3,5,3-Triiodothyronine (thyroid hormone)

Tcf4:

Transcription factor 4

YY1:

Ying Yang 1

References

  • Agius E, Soukkarieh C, Danesin C et al (2004) Converse control of oligodendrocyte and astrocyte lineage development by Sonic hedgehog in the chick spinal cord. Dev Biol 270:308–321

    PubMed  CAS  Google Scholar 

  • Aguayo AJ, Charron L, Bray GM (1976) Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and radiographic study. J Neurocytol 5:565–573

    PubMed  CAS  Google Scholar 

  • Aguayo AJ, Attiwell M, Trecarten J et al (1977) Abnormal myelination in transplanted Trembler mouse Schwann cells. Nature 265:73–75

    PubMed  CAS  Google Scholar 

  • Allen NJ, Barres BA (2009) Neuroscience: Glia—more than just brain glue. Nature 457:675–677

    PubMed  CAS  Google Scholar 

  • Amariglio N, Hirshberg A, Scheithauer BW et al (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6:e1000029

    Google Scholar 

  • Archer DR, Cuddon PA, Lipsitz D et al (1997) Myelination of the canine central nervous system by glial cell transplantation: a model for repair of human myelin disease. Nat Med 3:54–59

    PubMed  CAS  Google Scholar 

  • Baas D, Bourbeau D, Sarlieve LL et al (1997) Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone. Glia 19:324–332

    PubMed  CAS  Google Scholar 

  • Barres BA, Hart IK, Coles HS et al (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70:31–46

    PubMed  CAS  Google Scholar 

  • Barres BA, Jacobson MD, Schmid R et al (1993a) Does oligodendrocyte survival depend on axons? Curr Biol 3:489–497

    PubMed  CAS  Google Scholar 

  • Barres BA, Schmid R, Sendnter M et al (1993b) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295

    PubMed  CAS  Google Scholar 

  • Barres BA, Lazar MA, Raff MC (1994) A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120:1097–1108

    PubMed  CAS  Google Scholar 

  • Bauer NG, Richter-Landsberg C, Ffrench-Constant C (2009) Role of the oligodendroglial cytoskeleton in differentiation and myelination. Glia 57:1691–1705

    PubMed  Google Scholar 

  • Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81:871–927

    PubMed  CAS  Google Scholar 

  • Blakemore WF (1977) Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve. Nature 266:68–69

    PubMed  CAS  Google Scholar 

  • Blakemore WF, Crang AJ (1988) Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system. Dev Neurosci 10:1–11

    PubMed  CAS  Google Scholar 

  • Bradl M, Lassmann H (2010) Oligodendrocytes: biology and pathology. Acta Neuropathol 119:37–53

    PubMed  Google Scholar 

  • Bremer J, Baumann F, Tiberi C et al (2010) Axonal prion protein is required for peripheral myelin maintenance. Nat Neurosci 13:310–318

    PubMed  CAS  Google Scholar 

  • Burt RK, Loh Y, Pearce W et al (2008) Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 299:925–936

    PubMed  CAS  Google Scholar 

  • Butt AM, Kiff J, Hubbard P et al (2002) Synantocytes: new functions for novel NG2 expressing glia. J Neurocytol 31:551–565

    PubMed  CAS  Google Scholar 

  • Cai J, Qi Y, Hu X et al (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45:41–53

    PubMed  CAS  Google Scholar 

  • Campagnoni AT, Skoff RP (2001) The pathobiology of myelin mutants reveal novel biological functions of the MBP and PLP genes. Brain Pathol 11:74–91

    PubMed  CAS  Google Scholar 

  • Cao XY, Jiang XM, Dou ZH et al (1994) Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. N Engl J Med 331:1739–1744

    PubMed  CAS  Google Scholar 

  • Cao Q, Xu XM, Devries WH et al (2005) Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci 25:6947–6957

    PubMed  CAS  Google Scholar 

  • Cao Q, He Q, Wang Y et al (2010) Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury. J Neurosci 30:2989–3001

    PubMed  CAS  Google Scholar 

  • Chen Y, Balasubramaniyan V, Peng J et al (2007) Isolation and culture of rat and mouse oligodendrocyte precursor cells. Nat Protoc 2:1044–1051

    PubMed  CAS  Google Scholar 

  • Chomiak T, Hu B (2009) What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach. PLoS ONE 4:e7754

    PubMed  Google Scholar 

  • Chow SY, Moul J, Tobias CA et al (2000) Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord. Brain Res 874:87–106

    PubMed  CAS  Google Scholar 

  • Cohen RI, Rottkamp DM, Maric D et al (2003) A role for semaphorins and neuropilins in oligodendrocyte guidance. J Neurochem 85:1262–1278

    PubMed  CAS  Google Scholar 

  • Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231

    PubMed  Google Scholar 

  • Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17:83–93

    PubMed  CAS  Google Scholar 

  • Cotter L, Ozcelik M, Jacob C et al (2010) Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination. Science 328:1415–1418

    PubMed  CAS  Google Scholar 

  • Crang AJ, Blakemore WF (1989) The effect of the number of oligodendrocytes transplanted into X-irradiated, glial-free lesions on the extent of oligodendrocyte remyelination. Neurosci Lett 103:269–274

    PubMed  CAS  Google Scholar 

  • Crang AJ, Franklin RJ, Blakemore WF et al (1991) Transplantation of normal and genetically engineered glia into areas of demyelination. Ann N Y Acad Sci 633:563–565

    PubMed  CAS  Google Scholar 

  • Crang AJ, Gilson JM, Li WW et al (2004) The remyelinating potential and in vitro differentiation of MOG-expressing oligodendrocyte precursors isolated from the adult rat CNS. Eur J Neurosci 20:1445–1460

    PubMed  CAS  Google Scholar 

  • de Castro F, Bribian A (2005) The molecular orchestra of the migration of oligodendrocyte precursors during development. Brain Res Brain Res Rev 49:227–241

    PubMed  Google Scholar 

  • Debruin LS, Harauz G (2007) White matter rafting—membrane microdomains in myelin. Neurochem Res 32:213–228

    PubMed  CAS  Google Scholar 

  • Delange F (2000) The role of iodine in brain development. Proc Nutr Soc 59:75–79

    PubMed  CAS  Google Scholar 

  • Dugas JC, Cuellar TL, Scholze A et al (2010) Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron 65:597–611

    PubMed  CAS  Google Scholar 

  • Duncan ID, Hammang JP, Jackson KF et al (1988) Transplantation of oligodendrocytes and Schwann cells into the spinal cord of the myelin-deficient rat. J Neurocytol 17:351–360

    PubMed  CAS  Google Scholar 

  • Duncan ID, Goldman S, Macklin WB et al (2008) Stem cell therapy in multiple sclerosis: promise and controversy. Mult Scler 14:541–546

    PubMed  CAS  Google Scholar 

  • Ebner S, Dunbar M, McKinnon RD (2000) Distinct roles for PI3K in proliferation and survival of oligodendrocyte progenitor cells. J Neurosci Res 62:336–345

    PubMed  CAS  Google Scholar 

  • Einstein O, Grigoriadis N, Mizrachi-Kol R et al (2006) Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis. Exp Neurol 198:275–284

    PubMed  CAS  Google Scholar 

  • Faulkner J, Keirstead H (2005) Human embryonic stem cell-derived oligodendrocyte progenitors for the treatment of spinal cord injury. Transpl Immunol 15:131–142

    PubMed  CAS  Google Scholar 

  • Feldmann A, Winterstein C, White R et al (2009) Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes. J Neurosci Res 87:1760–1772

    PubMed  CAS  Google Scholar 

  • Feltri ML, Scherer SS, Wrabetz L et al (1992) Mitogen-expanded Schwann cells retain the capacity to myelinate regenerating axons after transplantation into rat sciatic nerve. Proc Natl Acad Sci USA 89:8827–8831

    PubMed  CAS  Google Scholar 

  • Flores AI, Mallon BS, Matsui T et al (2000) Akt-mediated survival of oligodendrocytes induced by neuregulins. J Neurosci 20:7622–7630

    PubMed  CAS  Google Scholar 

  • Franklin RJ, Blakemore WF (1997) Transplanting oligodendrocyte progenitors into the adult CNS. J Anat 190(Pt 1):23–33

    PubMed  Google Scholar 

  • Franklin RJM, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9:839–855

    PubMed  CAS  Google Scholar 

  • Frost EE, Zhou Z, Krasnesky K et al (2009) Initiation of oligodendrocyte progenitor cell migration by a PDGF-A activated extracellular regulated kinase (ERK) signaling pathway. Neurochem Res 34:169–181

    PubMed  CAS  Google Scholar 

  • Gansmuller A, Lachapelle F, Baron-Van Evercooren A et al (1986) Transplantations of newborn CNS fragments into the brain of shiverer mutant mice: extensive myelination by transplanted oligodendrocytes. II. Electron microscopic study. Dev Neurosci 8:197–207

    PubMed  CAS  Google Scholar 

  • Garwood J, Garcion E, Dobbertin A et al (2004) The extracellular matrix glycoprotein Tenascin-C is expressed by oligodendrocyte precursor cells and required for the regulation of maturation rate, survival and responsiveness to platelet-derived growth factor. Eur J Neurosci 20:2524–2540

    PubMed  Google Scholar 

  • German DC, Liang CL, Song T et al (2002) Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience 109:437–450

    PubMed  CAS  Google Scholar 

  • Gibney SM, Mcdermott KW (2009) Sonic hedgehog promotes the generation of myelin proteins by transplanted oligosphere-derived cells. J Neurosci Res 87:3067–3075

    PubMed  CAS  Google Scholar 

  • Goldman SA, Lang J, Roy N et al (2006) Progenitor cell-based myelination as a model for cell-based therapy of the central nervous system. Ernst Schering Res Found Workshop 60:195–213

    PubMed  CAS  Google Scholar 

  • Gould RM, Freund CM, Palmer F et al (2000) Messenger RNAs located in myelin sheath assembly sites. J Neurochem 75:1834–1844

    PubMed  CAS  Google Scholar 

  • Gravel M, Peterson J, Yong VW et al (1996) Overexpression of 2′,3′-cyclic nucleotide 3′-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination. Mol Cell Neurosci 7:453–466

    PubMed  CAS  Google Scholar 

  • Groves AK, Barnett SC, Franklin RJ et al (1993) Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362:453–455

    PubMed  CAS  Google Scholar 

  • Harauz G, Ladizhansky V, Boggs J (2009) Structural polymorphism and multifunctionality of myelin basic protein. Biochemistry 48:8094–8104

    PubMed  CAS  Google Scholar 

  • Harrington EP, Zhao C, Fancy SP et al (2010) Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination. Ann Neurol 68:703–716

    PubMed  CAS  Google Scholar 

  • Hauser S, Oksenberg J (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52:61–76

    PubMed  CAS  Google Scholar 

  • He Y, Dupree J, Wang J et al (2007) The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 55:217–230

    PubMed  CAS  Google Scholar 

  • Hofstetter CP, Holmström NA, Lilja JA et al (2005) Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 8:346–353

    PubMed  CAS  Google Scholar 

  • Hu BY, Du ZW, Zhang SC (2009) Differentiation of human oligodendrocytes from pluripotent stem cells. Nat Protoc 4:1614–1622

    PubMed  CAS  Google Scholar 

  • Hyun I, Lindvall O, Ahrlund-Richter L et al (2008) New ISSCR guidelines underscore major principles for responsible translational stem cell research. Cell Stem Cell 3:607–609

    PubMed  CAS  Google Scholar 

  • Ibarrola N, Rodriguez-Pena A (1997) Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development. Brain Res 752:285–293

    PubMed  CAS  Google Scholar 

  • Ishibashi T, Dakin KA, Stevens B et al (2006) Astrocytes promote myelination in response to electrical impulses. Neuron 49:823–832

    PubMed  CAS  Google Scholar 

  • Ishii A, Dutta R, Wark GM et al (2009) Human myelin proteome and comparative analysis with mouse myelin. Proc Natl Acad Sci USA 106:14605–14610

    PubMed  CAS  Google Scholar 

  • Izrael M, Zhang P, Kaufman R et al (2007) Human oligodendrocytes derived from embryonic stem cells: effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci 34:310–323

    PubMed  CAS  Google Scholar 

  • Jahn O, Tenzer S, Werner HB (2009) Myelin proteomics: molecular anatomy of an insulating sheath. Mol Neurobiol 40:55–72

    PubMed  CAS  Google Scholar 

  • John GR, Shankar SL, Shafit-Zagardo B et al (2002) Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8:1115–1121

    PubMed  CAS  Google Scholar 

  • Karim SA, Barrie JA, McCulloch MC et al (2007) PLP overexpression perturbs myelin protein composition and myelination in a mouse model of Pelizaeus-Merzbacher disease. Glia 55:341–351

    PubMed  Google Scholar 

  • Keirstead HS (2005) Stem cells for the treatment of myelin loss. Trends Neurosci 28:677–683

    PubMed  CAS  Google Scholar 

  • Keirstead HS, Nistor G, Bernal G et al (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705

    PubMed  CAS  Google Scholar 

  • Kemp K, Mallam E, Scolding N et al (2010) Stem cells in genetic myelin disorders. Regen Med 5:425–439

    PubMed  CAS  Google Scholar 

  • Kennea N, Waddington S, Chan J et al (2009) Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype. Cell Cycle 8:1069–1079

    PubMed  CAS  Google Scholar 

  • Kessaris N, Fogarty M, Iannarelli P et al (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9:173–179

    PubMed  CAS  Google Scholar 

  • Kiatpongsan S, Sipp D (2009) Medicine. Monitoring and regulating offshore stem cell clinics. Science 323:1564–1565

    PubMed  CAS  Google Scholar 

  • Lachapelle F, Gumpel M, Baulac M et al (1983) Transplantation of CNS fragments into the brain of shiverer mutant mice: extensive myelination by implanted oligodendrocytes. I. Immunohistochemical studies. Dev Neurosci 6:325–334

    PubMed  Google Scholar 

  • Larocca JN, Rodriguez-Gabin AG (2002) Myelin biogenesis: vesicle transport in oligodendrocytes. Neurochem Res 27:1313–1329

    PubMed  CAS  Google Scholar 

  • Learish RD, Brüstle O, Zhang SC et al (1999) Intraventricular transplantation of oligodendrocyte progenitors into a fetal myelin mutant results in widespread formation of myelin. Ann Neurol 46:716–722

    PubMed  CAS  Google Scholar 

  • Lee WC, Courtenay A, Troendle FJ et al (2005) Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy. FASEB J 19:1549–1551

    PubMed  CAS  Google Scholar 

  • Li QM, Fu YM, Shan ZY et al (2009) MSCs guide neurite directional extension and promote oligodendrogenesis in NSCs. Biochem Biophys Res Commun 384:372–377

    PubMed  CAS  Google Scholar 

  • Linker RA, Brechlin P, Jesse S et al (2009) Proteome profiling in murine models of multiple sclerosis: identification of stage specific markers and culprits for tissue damage. PLoS One 4:e7624

    PubMed  Google Scholar 

  • Lu QR, Yuk D, Alberta JA et al (2000) Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25:317–329

    PubMed  CAS  Google Scholar 

  • Maier O, Hoekstra D, Baron W (2008) Polarity development in oligodendrocytes: sorting and trafficking of myelin components. J Mol Neurosci 35:35–53

    PubMed  CAS  Google Scholar 

  • Martini R, Schachner M (1997) Molecular bases of myelin formation as revealed by investigations on mice deficient in glial cell surface molecules. Glia 19:298–310

    PubMed  CAS  Google Scholar 

  • McTigue DM, Tripathi RB (2008) The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem 107:1–19

    PubMed  CAS  Google Scholar 

  • Merrill JE (2009) In vitro and in vivo pharmacological models to assess demyelination and remyelination. Neuropsychopharmacology 34:55–73

    PubMed  CAS  Google Scholar 

  • Milward EA, Lundberg CG, Ge B et al (1997) Isolation and transplantation of multipotential populations of epidermal growth factor-responsive, neural progenitor cells from the canine brain. J Neurosci Res 50:862–871

    PubMed  CAS  Google Scholar 

  • Miyamoto Y, Yamauchi J, Tanoue A (2008) Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn. J Neurosci 28:8326–8337

    PubMed  CAS  Google Scholar 

  • Montag D, Giese KP, Bartsch U et al (1994) Mice deficient for the myelin-associated glycoprotein show subtle abnormalities in myelin. Neuron 13:229–246

    PubMed  CAS  Google Scholar 

  • Mothe AJ, Kulbatski I, Parr A et al (2008) Adult spinal cord stem/progenitor cells transplanted as neurospheres preferentially differentiate into oligodendrocytes in the adult rat spinal cord. Cell Transplant 17:735–751

    PubMed  Google Scholar 

  • Murtie JC, Macklin WB, Corfas G (2007) Morphometric analysis of oligodendrocytes in the adult mouse frontal cortex. J Neurosci Res 85:2080–2086

    PubMed  CAS  Google Scholar 

  • Narayanan SP, Flores AI, Wang F et al (2009) Akt signals through the mammalian target of rapamycin pathway to regulate CNS myelination. J Neurosci 29:6860–6870

    PubMed  CAS  Google Scholar 

  • Nave K-A, Salzer JL (2006) Axonal regulation of myelination by neuregulin 1. Curr Opin Neurobiol 16:492–500

    PubMed  CAS  Google Scholar 

  • Nave KA, Trapp BD (2008) Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci 31:535–561

    PubMed  CAS  Google Scholar 

  • Nishiyama A, Komitova M, Suzuki R et al (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22

    PubMed  CAS  Google Scholar 

  • Nistor GI, Totoiu MO, Haque N et al (2004) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396

    Google Scholar 

  • O’Leary MT, Blakemore WF (1997) Use of a rat Y chromosome probe to determine the long-term survival of glial cells transplanted into areas of CNS demyelination. J Neurocytol 26:191–206

    PubMed  Google Scholar 

  • Padovani-Claudio DA, Liu L, Ransohoff RM et al (2006) Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2. Glia 54:471–483

    PubMed  Google Scholar 

  • Paez PM, Fulton DJ, Spreuer V et al (2009) Golli myelin basic proteins regulate oligodendroglial progenitor cell migration through voltage-gated Ca2+ influx. J Neurosci 29:6663–6676

    PubMed  CAS  Google Scholar 

  • Park J, Liu B, Chen T et al (2008) Disruption of Nectin-like 1 cell adhesion molecule leads to delayed axonal myelination in the CNS. J Neurosci 28:12815–12819

    PubMed  CAS  Google Scholar 

  • Pastores GM (2009) Krabbe disease: an overview. Int J Clin Pharmacol Ther 47(Suppl 1):S75–S81

    PubMed  CAS  Google Scholar 

  • Patoine B (2009) NerveCenter: media focus on ‘miracle cure’ for cerebral palsy pits science vs. hype. Ann Neurol 66:A9–A11

    PubMed  Google Scholar 

  • Peake KB, Vance JE (2010) Defective cholesterol trafficking in Niemann-Pick C-deficient cells. FEBS Lett 584:2731–2739

    PubMed  CAS  Google Scholar 

  • Pellegatta S, Tunici P, Poliani PL et al (2006) The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation. Neurobiol Dis 21:314–323

    PubMed  CAS  Google Scholar 

  • Pellissier F, Gerber A, Bauer C et al (2007) The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion. BMC Neurosci 8:90

    PubMed  Google Scholar 

  • Petryniak MA, Potter GB, Rowitch DH et al (2007) Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 55:417–433

    PubMed  CAS  Google Scholar 

  • Pfeiffer SE, Warrington AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191–197

    PubMed  CAS  Google Scholar 

  • Pluchino S, Quattrini A, Brambilla E et al (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422:688–694

    PubMed  CAS  Google Scholar 

  • Poliak S, Peles E (2003) The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci 4:968–980

    PubMed  CAS  Google Scholar 

  • Rao MS (1999) Multipotent and restricted precursors in the central nervous system. Anat Rec 257:137–148

    PubMed  CAS  Google Scholar 

  • Rasband MN, Tayler J, Kaga Y et al (2005) CNP is required for maintenance of axon-glia interactions at nodes of Ranvier in the CNS. Glia 50:86–90

    PubMed  Google Scholar 

  • Readhead C, Hood L (1990) The dysmyelinating mouse mutations shiverer (shi) and myelin deficient (shimld). Behav Genet 20:213–234

    PubMed  CAS  Google Scholar 

  • Richter MW, Roskams AJ (2008) Olfactory ensheathing cell transplantation following spinal cord injury: hype or hope? Exp Neurol 209:353–367

    PubMed  Google Scholar 

  • Rivera FJ, Kandasamy M, Couillard-Despres S et al (2008) Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors. J Neurochem 107:832–843

    PubMed  CAS  Google Scholar 

  • Rodríguez-Peña A (1999) Oligodendrocyte development and thyroid hormone. J Neurobiol 40:497–512

    PubMed  Google Scholar 

  • Romanelli RJ, Mahajan KR, Fulmer CG et al (2009) Insulin-like growth factor-I-stimulated Akt phosphorylation and oligodendrocyte progenitor cell survival require cholesterol-enriched membranes. J Neurosci Res 87:3369–3377

    PubMed  CAS  Google Scholar 

  • Rosenberg SS, Kelland EE, Tokar E et al (2008) The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation. Proc Natl Acad Sci USA 105:14662–14667

    PubMed  CAS  Google Scholar 

  • Rowitch DH (2004) Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5:409–419

    PubMed  CAS  Google Scholar 

  • Royland JE, Wiggins RC, Konat GW (1992) Myelin isolation: comparison of sedimentation and flotation techniques. Neurochem Int 21:171–175

    PubMed  CAS  Google Scholar 

  • Ryan KA, Sanders AN, Wang DD et al (2010) Tracking the rise of stem cell tourism. Regen Med 5:27–33

    PubMed  CAS  Google Scholar 

  • Sabri MI, Bone AH, Davison AN (1974) Turnover of myelin and other structural proteins in the developing rat brain. Biochem J 142:499–507

    PubMed  CAS  Google Scholar 

  • Saher G, Brugger B, Lappe-Siefke C et al (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8:468–475

    PubMed  CAS  Google Scholar 

  • Sarliève LL, Rodríguez-Peña A, Langley K (2004) Expression of thyroid hormone receptor isoforms in the oligodendrocyte lineage. Neurochem Res 29:903–922

    PubMed  Google Scholar 

  • Sarret C, Combes P, Micheau P et al (2010) Novel neuronal proteolipid protein isoforms encoded by the human myelin proteolipid protein 1 gene. Neuroscience 166:522–538

    PubMed  CAS  Google Scholar 

  • Sasaki M, Black JA, Lankford KL et al (2006) Molecular reconstruction of nodes of Ranvier after remyelination by transplanted olfactory ensheathing cells in the demyelinated spinal cord. J Neurosci 26:1803–1812

    PubMed  CAS  Google Scholar 

  • Schafer DP, Rasband MN (2006) Glial regulation of the axonal membrane at nodes of Ranvier. Curr Opin Neurobiol 16:508–514

    PubMed  CAS  Google Scholar 

  • Sharp J, Frame J, Siegenthaler M et al (2009) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 28:152–163

    Google Scholar 

  • Sherman DL, Brophy PJ (2005) Mechanisms of axon ensheathment and myelin growth. Nat Rev Neurosci 6:683–690

    PubMed  CAS  Google Scholar 

  • Simpson PB, Armstrong RC (1999) Intracellular signals and cytoskeletal elements involved in oligodendrocyte progenitor migration. Glia 26:22–35

    PubMed  CAS  Google Scholar 

  • Skundric DS (2005) Experimental models of relapsing-remitting multiple sclerosis: current concepts and perspective. Curr Neurovasc Res 2:349–362

    PubMed  CAS  Google Scholar 

  • Spassky N, de Castro F, Le Bras B et al (2002) Directional guidance of oligodendroglial migration by class 3 semaphorins and netrin-1. J Neurosci 22:5992–6004

    PubMed  CAS  Google Scholar 

  • Steinman L, Martin R, Bernard C et al (2002) Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu Rev Neurosci 25:491–505

    PubMed  CAS  Google Scholar 

  • Stevens B, Porta S, Haak LL et al (2002) Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36:855–868

    PubMed  CAS  Google Scholar 

  • Storch MK, Stefferl A, Brehm U et al (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 8:681–694

    PubMed  CAS  Google Scholar 

  • Strazza M, Luddi A, Carbone M et al (2009) Significant correction of pathology in brains of twitcher mice following injection of genetically modified mouse neural progenitor cells. Mol Genet Metab 97:27–34

    PubMed  CAS  Google Scholar 

  • Timsit S, Martinez S, Allinquant B et al (1995) Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. J Neurosci 15:1012–1024

    PubMed  CAS  Google Scholar 

  • Tontsch U, Archer DR, Dubois-Dalcq M et al (1994) Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc Natl Acad Sci USA 91:11616–11620

    PubMed  CAS  Google Scholar 

  • Trapp BD, Moench T, Pulley M et al (1987) Spatial segregation of mRNA encoding myelin-specific proteins. Proc Natl Acad Sci USA 84:7773–7777

    PubMed  CAS  Google Scholar 

  • Trapp BD, Bernier L, Andrews SB et al (1988) Cellular and subcellular distribution of 2′,3′-cyclic nucleotide 3′-phosphodiesterase and its mRNA in the rat central nervous system. J Neurochem 51:859–868

    PubMed  CAS  Google Scholar 

  • Trotter J, Crang AJ, Schachner M et al (1993) Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system. Glia 9:25–40

    PubMed  CAS  Google Scholar 

  • Trotter J, Karram K, Nishiyama A (2010) NG2 cells: properties, progeny and origin. Brain Res Rev 63:72–82

    PubMed  CAS  Google Scholar 

  • Tsai H-H, Frost E, To V et al (2002) The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell 110:373–383

    PubMed  CAS  Google Scholar 

  • Tyler WA, Gangoli N, Gokina P et al (2009) Activation of the mammalian target of rapamycin (mTOR) is essential for oligodendrocyte differentiation. J Neurosci 29:6367–6378

    PubMed  CAS  Google Scholar 

  • Virchow R (1846) Ueber das granulirte Aussehen der Wandungen der Gehirnventrikel. Allg Z Psychiat 3:242–250

    Google Scholar 

  • Vroemen M, Aigner L, Winkler J et al (2003) Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways. Eur J Neurosci 18:743–751

    PubMed  Google Scholar 

  • Waxman SG, Sims TJ (1984) Specificity in central myelination: evidence for local regulation of myelin thickness. Brain Res 292:179–185

    PubMed  CAS  Google Scholar 

  • Windrem M, Nunes M, Rashbaum W et al (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 10:93–97

    PubMed  CAS  Google Scholar 

  • Windrem MS, Schanz SJ, Guo M et al (2008) Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell 2:553–565

    PubMed  CAS  Google Scholar 

  • Ye F, Chen Y, Hoang T et al (2009) HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci 12:829–838

    PubMed  CAS  Google Scholar 

  • Zalc B (2006) The acquisition of myelin: a success story. Novartis Found Symp 276:15–21 (discussion 21–25, 54–57, 275–281)

    Google Scholar 

  • Zhang PL, Izrael M, Ainbinder E et al (2006) Increased myelinating capacity of embryonic stem cell derived oligodendrocyte precursors after treatment by interleukin-6/soluble interleukin-6 receptor fusion protein. Mol Cell Neurosci 31:387–398

    PubMed  CAS  Google Scholar 

  • Zhang Y, Argaw AT, Gurfein BT et al (2009) Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination. Proc Natl Acad Sci USA 106:19162–19167

    PubMed  CAS  Google Scholar 

  • Zhao X, He X, Han X et al (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65:612–626

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We regret that the essential work of many investigators could not be included in this review due to space constraints. We wish to thank our funding support: California Institute for Regenerative Medicine Postdoctoral Training Grant (G.B. Potter), NIH K08 NS062744 (M.A. Petryniak), and Howard Hughes Medical Institute (D.H. Rowitch).

Author information

Authors and Affiliations

  1. Department of Pediatrics, UCSF, 513 Parnassus Avenue, San Francisco, CA, 94143-0525, USA

    Gregory B. Potter, David H. Rowitch & Magdalena A. Petryniak

  2. Department of Neurological Surgery, UCSF, 513 Parnassus Avenue, San Francisco, CA, 94143-0525, USA

    David H. Rowitch

  3. Howard Hughes Medical Institute, UCSF, 513 Parnassus Avenue, San Francisco, CA, 94143-0525, USA

    David H. Rowitch

Authors
  1. Gregory B. Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David H. Rowitch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Magdalena A. Petryniak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to David H. Rowitch or Magdalena A. Petryniak.

About this article

Cite this article

Potter, G.B., Rowitch, D.H. & Petryniak, M.A. Myelin Restoration: Progress and Prospects for Human Cell Replacement Therapies. Arch. Immunol. Ther. Exp. 59, 179–193 (2011). https://doi.org/10.1007/s00005-011-0120-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-011-0120-7

Keywords

Search

Navigation