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