Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro

Juliana Redondo, Pamela Sarkar, Kevin Kemp, Paul F. Virgo, Joya Pawade, Aimie Norton, David C. Emery, Martin G. Guttridge, David I. Marks, Alastair Wilkins, Neil J. Scolding, Claire M. Rice*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

9 Citations (Scopus)
297 Downloads (Pure)

Abstract

Background: Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. Objectives: To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Methods: Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. Results: In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Conclusion: Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS.

Original languageEnglish
Pages (from-to)919-931
Number of pages13
JournalMultiple Sclerosis Journal
Volume24
Issue number7
Early online date26 May 2017
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • bone marrow
  • Cell therapy
  • mesenchymal stromal cell
  • multiple sclerosis

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