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

• Published in: Multiple sclerosis Vol. 24; no. 7; pp. 919 - 931
• Main Authors: Redondo, Juliana, Sarkar, Pamela, Kemp, Kevin, Virgo, Paul F, Pawade, Joya, Norton, Aimie, Emery, David C, Guttridge, Martin G, Marks, David I, Wilkins, Alastair, Scolding, Neil J, Rice, Claire M
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2018
• Subjects: Adult; Cell Proliferation - physiology; Cells, Cultured; Cellular Senescence - physiology; Female; Humans; Male; Mesenchymal Stem Cells - pathology; Middle Aged; Multiple Sclerosis - pathology; Stem Cell Niche - physiology; Cell therapy; mesenchymal stromal cell; multiple sclerosis; bone marrow
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458517711276

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.