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.
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