Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.
CNS stem and progenitor cells
aging
cell therapy
mesenchymal stem cells
multiple sclerosis
oligodendrocytes
remyelination
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
30
08
2018
revised:
26
03
2019
accepted:
29
03
2019
pubmed:
1
5
2019
medline:
11
2
2020
entrez:
1
5
2019
Statut:
ppublish
Résumé
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.
Identifiants
pubmed: 31038798
doi: 10.1002/glia.23624
pmc: PMC6618006
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1510-1525Subventions
Organisme : Medical Research Council
ID : G0701476
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300336
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M010503/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0802545
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300338
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700392
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K008803/1
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Glia published by Wiley Periodicals, Inc.
Références
J Neurochem. 2008 Nov;107(3):832-43
pubmed: 18786165
Stem Cells. 2006 Oct;24(10):2209-19
pubmed: 16763198
Lancet Neurol. 2012 Feb;11(2):150-6
pubmed: 22236384
PLoS One. 2012;7(9):e45052
pubmed: 23028757
Nat Neurosci. 2012 Jun;15(6):862-70
pubmed: 22610068
Lancet. 2008 Oct 25;372(9648):1502-17
pubmed: 18970977
Exp Biol Med (Maywood). 2001 Jun;226(6):507-20
pubmed: 11395921
Exp Neurol. 2011 Jul;230(1):138-48
pubmed: 21515259
Cell Transplant. 2011;20(1):5-14
pubmed: 21396235
Glia. 2018 Jan;66(1):145-160
pubmed: 28940767
J Neurosci Res. 2004 Oct 15;78(2):157-66
pubmed: 15378614
Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1531-6
pubmed: 21205896
Lab Invest. 2003 Jul;83(7):949-62
pubmed: 12861035
Nat Neurosci. 2013 Sep;16(9):1211-1218
pubmed: 23872599
Exp Aging Res. 1976 Sep;2(5):399-407
pubmed: 1035163
Glia. 2019 Aug;67(8):1510-1525
pubmed: 31038798
Glia. 1999 Oct;28(1):77-83
pubmed: 10498825
Cell Stem Cell. 2012 Jan 6;10(1):96-103
pubmed: 22226359
J Cell Biol. 2015 Dec 7;211(5):975-85
pubmed: 26644513
Nat Neurosci. 2008 Sep;11(9):1024-34
pubmed: 19160500
Nat Rev Neurosci. 2008 Nov;9(11):839-55
pubmed: 18931697
Stem Cells. 2004;22(5):675-82
pubmed: 15342932
J Cell Biol. 1980 Jun;85(3):890-902
pubmed: 6248568
Glia. 2012 Jan;60(1):1-12
pubmed: 21858876
Glia. 2004 May;46(3):311-22
pubmed: 15048854
Cell Stem Cell. 2010 Jun 4;6(6):578-90
pubmed: 20569695
Nat Rev Neurosci. 2017 Nov 16;18(12):753-769
pubmed: 29142295
Cell Physiol Biochem. 2009;24(3-4):317-24
pubmed: 19710546
Stem Cells Dev. 2012 Jul 20;21(11):1838-51
pubmed: 22074360
Cell Death Dis. 2013 Aug 29;4:e779
pubmed: 23990019
Cell Transplant. 2008;17(7):865-73
pubmed: 19044212
Curr Pharm Des. 2012;18(13):1694-717
pubmed: 22352749
PLoS One. 2013 Aug 12;8(8):e71814
pubmed: 23951248
Glia. 2009 Aug 15;57(11):1192-203
pubmed: 19191336
N Engl J Med. 2018 Jan 11;378(2):169-180
pubmed: 29320652
Glia. 1999 Feb 1;25(3):216-28
pubmed: 9932868
Stem Cell Res. 2012 Mar;8(2):215-25
pubmed: 22265741
Cell Tissue Res. 2012 Jul;349(1):331-47
pubmed: 22322424
J Neurosci. 2002 Apr 1;22(7):2451-9
pubmed: 11923409
Mult Scler. 2010 Apr;16(4):503-10
pubmed: 20086020
Nat Neurosci. 2011 Jan;14(1):45-53
pubmed: 21131950