Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.
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Authors
Wodnar, Roman
Feichtner, Martina
Lange, Simona
Errea, Oihana
O'Sullivan, Anna
Brachtl, Gabriele
Greil, Richard
Tempfer, Herbert
Publication Date
2019-08Journal Title
Glia
ISSN
0894-1491
Publisher
John Wiley & Sons Inc.
Volume
67
Issue
8
Pages
1510-1525
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Rivera, F. J., de la Fuente, A. G., Zhao, C., Silva, M. E., Gonzalez, G. A., Wodnar, R., Feichtner, M., et al. (2019). Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.. Glia, 67 (8), 1510-1525. https://doi.org/10.1002/glia.23624
Abstract
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 prooligodendrogenic
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 myelin-like sheaths. These findings may
impact on the design of therapies using autologous MSCs in older MS patients.
Keywords
Oligodendroglia, Cells, Cultured, Mesenchymal Stem Cells, Animals, Rats, Inbred F344, Rats, Sprague-Dawley, Demyelinating Diseases, Disease Models, Animal, Tissue Culture Techniques, Aging, Female, Male, Remyelination
Sponsorship
The authors would like to thank the following funding agencies for their support: Paracelsus Medical University PMU-FFF Long-Term Fellowship L-12/01/001-RIV (to and Stand-Alone Grant E-12/15/077-RIT (both to F.J.R.); Chilean Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) FONDECYT Program Regular Grant Nº 1161787 (to F.J.R.), Regular Grant Nº 1141015 (to L.F.B.); Chilean CONICYT PCI Program Grant Nº REDES170233 (to F.J.R.), Grant Nº REDES180139 and Grant Nº REDI170037; Chilean CONICYT FONDEFIDeA Program Grant Nº ID17AM0043 (to M.E.S. and F.J.R.); European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements N HEALTH-F2-2011-278850 (INMiND) and HEALTH-F2-2011-279288 (IDEA). The
work in the Küry laboratory was supported by the German Research Foundation (DFG; KU1934/2_1, KU1934/5-1) and the Christiane and Claudia Hempel Foundation for clinical and iBrain. The work in the Franklin laboratory was supported by grants from the UK Multiple Sclerosis Society and the Adelson Medical Research Foundation, and a core support grant from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. In addition, the present work was supported by the state of Salzburg (to L.A.). We thank Armin Schneider, Sygnis Pharma AG Heidelberg, Germany, for the MBP promoter construct. We disclose any conflict of interest.
Funder references
MRC (MC_PC_12009)
Identifiers
External DOI: https://doi.org/10.1002/glia.23624
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291748
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