Myelin Restoration: Progress and Prospects for Human Cell Replacement Therapies

REVIEW

DOI: 10.1007/s00005-011-0120-7

Cite this article as:
Potter, G.B., Rowitch, D.H. & Petryniak, M.A. Arch. Immunol. Ther. Exp. (2011) 59: 179. doi:10.1007/s00005-011-0120-7

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.

Keywords

Myelin Transplantation Oligodendrocyte Development Pelizaeus–Merzbacher disease Cell-replacement Leukodystrophy 

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

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2011

Authors and Affiliations

  1. 1.Department of PediatricsUCSFSan FranciscoUSA
  2. 2.Department of Neurological SurgeryUCSFSan FranciscoUSA
  3. 3.Howard Hughes Medical InstituteUCSFSan FranciscoUSA

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