title: Cell therapy in demyelinating diseases.
abstract: Multiple sclerosis presents particular and serious problems to those attempting to develop cell-based therapies: the occurrence of innumerable lesions scattered throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory process, to name but a few. Nevertheless, the limited and relatively focused nature of damage to oligodendrocytes and myelin, at least in early disease, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that therapies may be possible. Here, we review the clinical and biological problems presented by multiple sclerosis in the context of cell therapies, and the neuroscientific background to the development of strategies for myelin repair. We attempt to highlight those areas where difficulties have yet to be resolved and draw on a variety of more recent experimental findings to speculate on how remyelinating therapies are likely to develop in the foreseeable future.
authors.affiliation: University of Bristol Institute of Clinical Neurosciences, Department of Neurology, Frenchay Hospital, Bristol, BS16 1LE, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Rice
authors.forename: Christopher
authors.initials: C
authors.lastname: Halfpenny
authors.forename: Neil
authors.initials: N
authors.lastname: Scolding
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D003711:Demyelinating Diseases / Q000628:therapy*; D006801:Humans; D009103:Multiple Sclerosis / Q000628:therapy; D009417:Nerve Tissue / Q000166:cytology / Q000637:transplantation; D009474:Neurons / Q000637:transplantation
references.citation: Lancet Neurol. 2002 Jun;1(2):92-100
references.pmid: 12849513
references.citation: Int J Neurosci. 2003 Jul;113(7):945-56
references.pmid: 12881187
references.citation: N Engl J Med. 2003 Aug 7;349(6):570-82
references.pmid: 12904523
references.citation: Nat Med. 2004 Jan;10(1):93-7
references.pmid: 14702638
references.citation: Nat Biotechnol. 2004 Jan;22(1):53-4
references.pmid: 14661028
references.citation: Lancet. 2004 Jul 10-16;364(9429):193-9
references.pmid: 15246733
references.citation: Neurology. 1975 Aug;25(8):713-6
references.pmid: 1171404
references.citation: Ann Neurol. 1979 Jan;5(1):22-31
references.pmid: 426466
references.citation: J Neurol Sci. 1980 Apr;46(1):63-81
references.pmid: 7373344
references.citation: Lab Invest. 1981 Dec;45(6):534-46
references.pmid: 7321526
references.citation: Ann Neurol. 1983 Sep;14(3):339-46
references.pmid: 6195956
references.citation: J Neurol Sci. 1985 Feb;67(2):143-59
references.pmid: 3981217
references.citation: J Clin Invest. 2003 Mar;111(6):843-50
references.pmid: 12639990
references.citation: Blood. 2003 Apr 15;101(8):2999-3001
references.pmid: 12480709
references.citation: Lancet. 2003 Mar 29;361(9363):1084-8
references.pmid: 12672312
references.citation: Nature. 2003 Apr 17;422(6933):688-94
references.pmid: 12700753
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):53-7
references.pmid: 8278406
references.citation: Int J Dev Neurosci. 1993 Oct;11(5):641-9
references.pmid: 8116476
references.citation: Brain. 1994 Jun;117 ( Pt 3):563-78
references.pmid: 8032866
references.citation: Dev Suppl. 1993;:219-25
references.pmid: 8049477
references.citation: Neuropathol Appl Neurobiol. 1994 Apr;20(2):200-1
references.pmid: 8072661
references.citation: J Neurosci. 1999 Nov 15;19(22):9986-95
references.pmid: 10559406
references.citation: Mol Cell Neurosci. 1999 Oct-Nov;14(4-5):287-300
references.pmid: 10588385
references.citation: Philos Trans R Soc Lond B Biol Sci. 1999 Oct 29;354(1390):1649-73
references.pmid: 10603618
references.citation: Brain. 2000 Jan;123 ( Pt 1):105-15
references.pmid: 10611125
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15256-61
references.pmid: 10611372
references.citation: Science. 2000 Feb 25;287(5457):1442-6
references.pmid: 10688785
references.citation: Neuroreport. 1999 Dec 16;10(18):3961-5
references.pmid: 10716241
references.citation: Brain. 1986 Dec;109 ( Pt 6):1261-77
references.pmid: 3539257
references.citation: Proc Natl Acad Sci U S A. 1986 Dec;83(24):9774-8
references.pmid: 3025849
references.citation: Adv Neurol. 1988;47:215-54
references.pmid: 3278518
references.citation: J Neurocytol. 1988 Aug;17(4):521-9
references.pmid: 3193129
references.citation: Lab Invest. 1989 May;60(5):714-25
references.pmid: 2716284
references.citation: Lab Invest. 1989 Nov;61(5):489-503
references.pmid: 2811298
references.citation: J Neurosci. 1992 Apr;12(4):1538-47
references.pmid: 1556607
references.citation: Cell. 1992 Jul 10;70(1):31-46
references.pmid: 1623522
references.citation: Exp Neurol. 1994 Nov;130(1):41-52
references.pmid: 7821395
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1431-5
references.pmid: 7877996
references.citation: Brain Res. 1995 Feb 20;672(1-2):159-69
references.pmid: 7749738
references.citation: Neuroreport. 1995 Feb 15;6(3):441-5
references.pmid: 7766839
references.citation: Neuron. 1995 Oct;15(4):805-19
references.pmid: 7576630
references.citation: Nat Med. 1995 Jan;1(1):80-3
references.pmid: 7584959
references.citation: Cell Transplant. 2001;10(3):305-15
references.pmid: 11437076
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7841-5
references.pmid: 11427725
references.citation: Curr Opin Genet Dev. 2001 Oct;11(5):575-80
references.pmid: 11532401
references.citation: J Neuroimmunol. 2001 Oct 1;119(2):261-8
references.pmid: 11585629
references.citation: Blood. 2001 Nov 1;98(9):2615-25
references.pmid: 11675329
references.citation: Neurosci Lett. 2001 Dec18;316(2):67-70
references.pmid: 11742717
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2344-9
references.pmid: 11782534
references.citation: Gene Ther. 2002 May;9(10):613-24
references.pmid: 12032707
references.citation: Gene Ther. 2002 Jun;9(11):754-8
references.pmid: 12032704
references.citation: Nature. 2002 Jul 4;418(6893):41-9
references.pmid: 12077603
references.citation: Dev Neurosci. 1992;14(2):114-22
references.pmid: 1396171
references.citation: J Neurosci Res. 1993 Jan;34(1):1-13
references.pmid: 7678656
references.citation: Ann Neurol. 1993 Feb;33(2):137-51
references.pmid: 8434875
references.citation: Nature. 1993 Apr 1;362(6419):453-5
references.pmid: 8464477
references.citation: J Neuropathol Exp Neurol. 1993 May;52(3):199-204
references.pmid: 7684075
references.citation: Eur J Neurosci. 1993 Oct 1;5(10):1247-60
references.pmid: 8275227
references.citation: Mol Med Today. 1997 Dec;3(12):554-61
references.pmid: 9449127
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3908-13
references.pmid: 9520466
references.citation: Science. 1998 Jun 5;280(5369):1610-3
references.pmid: 9616125
references.citation: J Neurosci. 1998 Aug 15;18(16):6176-85
references.pmid: 9698311
references.citation: Lancet. 1998 Aug 1;352(9125):340-1
references.pmid: 9717917
references.citation: Brain. 1998 Dec;121 ( Pt 12):2221-8
references.pmid: 9874475
references.citation: Glia. 1999 Feb 1;25(3):216-28
references.pmid: 9932868
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4089-94
references.pmid: 10097168
references.citation: Baillieres Clin Neurol. 1997 Oct;6(3):525-48
references.pmid: 10101588
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: Neuroreport. 1999 Feb 25;10(3):535-40
references.pmid: 10208585
references.citation: Eur J Neurosci. 1999 May;11(5):1508-14
references.pmid: 10215903
references.citation: Exp Neurol. 1999 Apr;156(2):333-44
references.pmid: 10328940
references.citation: J Neuroimmunol. 1999 Jul 1;98(1):69-76
references.pmid: 10426364
references.citation: Nature. 2003 Apr 24;422(6934):897-901
references.pmid: 12665832
references.citation: Nature. 2003 Apr 24;422(6934):901-4
references.pmid: 12665833
references.citation: Nature. 2003 Apr 24;422(6934):823-5
references.pmid: 12712184
references.citation: J Neurosci. 2003 Jun 15;23(12):4967-74
references.pmid: 12832519
references.citation: Ann Neurol. 1995 Dec;38(6):901-9
references.pmid: 8526462
references.citation: Brain. 1995 Dec;118 ( Pt 6):1583-92
references.pmid: 8595487
references.citation: Exp Neurol. 1996 Feb;137(2):263-76
references.pmid: 8635541
references.citation: J Neurosci. 1996 May 15;16(10):3199-208
references.pmid: 8627358
references.citation: Acta Neuropathol. 1996;91(1):82-8
references.pmid: 8773151
references.citation: Neuropathol Appl Neurobiol. 1996 Jun;22(3):199-206
references.pmid: 8804021
references.citation: Glia. 1996 Jul;17(3):217-24
references.pmid: 8840163
references.citation: J Neurosci. 1996 Dec 1;16(23):7599-609
references.pmid: 8922416
references.citation: Glia. 1996 Feb;16(2):147-64
references.pmid: 8929902
references.citation: Nat Med. 1997 Jan;3(1):54-9
references.pmid: 8986741
references.citation: J Anat. 1997 Jan;190 ( Pt 1):23-33
references.pmid: 9034879
references.citation: Mult Scler. 1997 Apr;3(2):133-6
references.pmid: 9291167
references.citation: Mult Scler. 1997 Apr;3(2):157-61
references.pmid: 9291173
references.citation: Mult Scler. 1996 Jul;1(6):388-92
references.pmid: 9345424
references.citation: J Neuropathol Exp Neurol. 1997 Nov;56(11):1191-201
references.pmid: 9370229
references.citation: J Neurosci. 1998 Jan 15;18(2):601-9
references.pmid: 9425002
references.citation: Science. 2000 Dec 1;290(5497):1775-9
references.pmid: 11099418
references.citation: Science. 2000 Dec 1;290(5497):1779-82
references.pmid: 11099419
references.citation: Glia. 2000 Dec;32(3):214-25
references.pmid: 11102963
references.citation: Glia. 2000 Dec;32(3):264-70
references.pmid: 11102967
references.citation: Ann Neurol. 2000 Dec;48(6):893-901
references.pmid: 11117546
references.citation: Novartis Found Symp. 2000;231:7-15; discussion 16-20
references.pmid: 11131546
references.citation: Neurol Sci. 2000;21(4 Suppl 2):S889-91
references.pmid: 11205369
references.citation: Lancet. 2001 Feb 3;357(9253):329-30
references.pmid: 11210992
references.citation: J Neurosci. 2001 Feb 1;21(3):944-50
references.pmid: 11157080
references.citation: Biochem Biophys Res Commun. 2001 Mar 23;282(1):148-52
references.pmid: 11263984
references.citation: Bone Marrow Transplant. 2001 Feb;27(3):235-9
references.pmid: 11277170
references.citation: Stroke. 2001 Apr;32(4):1005-11
references.pmid: 11283404
references.citation: Neuropathol Appl Neurobiol. 2001 Feb;27(1):59-67
references.pmid: 11299003
references.citation: Brain. 2001 May;124(Pt 5):962-73
references.pmid: 11335698
references.citation: Cell. 2001 May 4;105(3):369-77
references.pmid: 11348593
references.citation: Curr Opin Neurol. 2001 Jun;14(3):271-8
references.pmid: 11371748
references.citation: Ann Neurol. 2001 Jun;49(6):776-85
references.pmid: 11409430
references.citation: Glia. 2001 Jul;35(1):26-34
references.pmid: 11424189
references.citation: Science. 1999 Jul 30;285(5428):754-6
references.pmid: 10427001
references.citation: Brain Res Bull. 1999 Aug;49(6):377-91
references.pmid: 10483914
references.citation: J Neurotrauma. 1999 Aug;16(8):695-703
references.pmid: 10511242
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11616-20
references.pmid: 7972113
references.citation: Mol Cell Neurosci. 2000 Mar;15(3):288-302
references.pmid: 10736205
references.citation: Nat Biotechnol. 2000 Apr;18(4):410-4
references.pmid: 10748521
references.citation: Glia. 2000 May;30(3):209-18
references.pmid: 10756071
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7585-90
references.pmid: 10840047
references.citation: Brain. 2000 Jun;123 ( Pt 6):1174-83
references.pmid: 10825356
references.citation: Am J Pathol. 2000 Jul;157(1):267-76
references.pmid: 10880396
references.citation: Brain. 2000 Aug;123 ( Pt 8):1581-8
references.pmid: 10908188
references.citation: Exp Neurol. 2000 Aug;164(2):247-56
references.pmid: 10915564
references.citation: J Neurosci Res. 2000 Aug 15;61(4):364-70
references.pmid: 10931522
references.citation: J Neurosci. 2000 Sep 1;20(17):6404-12
references.pmid: 10964946
references.citation: Exp Neurol. 2000 Oct;165(2):237-47
references.pmid: 10993684
references.citation: Neuroreport. 2000 Sep 11;11(13):3001-5
references.pmid: 11006983
references.citation: J Neurol Sci. 2000 Sep 1;178(1):10-6
references.pmid: 11018243
references.citation: Eur J Pharmacol. 2000 Sep 29;405(1-3):297-302
references.pmid: 11033336
references.citation: N Engl J Med. 2000 Nov 16;343(20):1430-8
references.pmid: 11078767
references.citation: Nat Med. 2000 Nov;6(11):1229-34
references.pmid: 11062533
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12846-51
references.pmid: 11070094
references.citation: Neuron. 2000 Oct;28(1):15-8
references.pmid: 11086978
references.citation: J Neurosci Res. 2002 Jun 1;68(5):501-10
references.pmid: 12111840
references.citation: J Pathol. 2002 Jul;197(4):441-56
references.pmid: 12115861
references.citation: Nat Biotechnol. 2002 Aug;20(8):791-2
references.pmid: 12148006
references.citation: J Neurosci. 2002 Aug 1;22(15):6623-30
references.pmid: 12151541
references.citation: Neuroreport. 2002 Jul 2;13(9):1185-8
references.pmid: 12151766
references.citation: Glia. 2002 Sep;39(3):229-36
references.pmid: 12203389
references.citation: Nature. 2002 Oct 3;419(6906):437
references.pmid: 12374136
references.citation: Blood. 2003 Mar 15;101(6):2215-8
references.pmid: 12433693