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Glia. 2019 Apr 30. doi: 10.1002/glia.23624. [Epub ahead of print]

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

Author information

1
Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
2
Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile.
3
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria.
4
Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
5
Wellcome-MRC Cambridge Stem Cell Institute & Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
6
Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile.
7
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Linz/Vienna, Austria.
8
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
9
Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
10
Laboratory of Experimental Ophthalmology, Department of Ophthalmology, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
11
Laboratory for Immunological and Molecular Cancer Research, 3rd Medical Department for Hematology, Medical Oncology, Hemostasiology, Infectious Diseases, and Rheumatology, Federal Hospital of Salzburg and Paracelsus Medical University, Salzburg, Austria.
12
Experimental and Clinical Cell Therapy Institute, Paracelsus Medical University, Salzburg, Austria.
13
Institute of Tendon and Bone Regeneration, Paracelsus Medical University, Salzburg, Austria.
14
Centro de Investigación Biomédica (CIB), Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
15
Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.

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.

KEYWORDS:

CNS stem and progenitor cells; aging; cell therapy; mesenchymal stem cells; multiple sclerosis; oligodendrocytes; remyelination

PMID:
31038798
DOI:
10.1002/glia.23624

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