Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination

Francisco J Rivera, Alerie G de la Fuente, Chao Zhao, Maria E Silva, Ginez A Gonzalez, Roman Wodnar, Martina Feichtner, Simona Lange, Oihana Errea, Eleni Priglinger, Anna O'Sullivan, Pasquale Romanelli, Janusz J Jadasz, Gabriele Brachtl, Richard Greil, Herbert Tempfer, Andreas Traweger, Luis F Bátiz, Patrick Küry, Sebastien Couillard-DespresRobin J M Franklin, Ludwig Aigner

Research output: Contribution to journalArticle

13 Citations (Scopus)
12 Downloads (Pure)

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 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.

Original languageEnglish
Pages (from-to)1510-1525
Number of pages16
JournalGlia
Volume67
Issue number8
DOIs
Publication statusPublished - Aug 2019

Bibliographical note

© 2019 The Authors. Glia published by Wiley Periodicals, Inc.

Keywords

  • Aging/physiology
  • Animals
  • Cells, Cultured
  • Demyelinating Diseases/physiopathology
  • Disease Models, Animal
  • Female
  • Male
  • Mesenchymal Stem Cells/physiology
  • Oligodendroglia/physiology
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Remyelination/physiology
  • Tissue Culture Techniques

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