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

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

In: Multiple Sclerosis Journal, Vol. 24, No. 7, 01.06.2018, p. 919-931.

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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. / Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro. In: Multiple Sclerosis Journal. 2018 ; Vol. 24, No. 7. pp. 919-931.

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@article{919fee95a5b04f879671ebd7a658657b,
title = "Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro",
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.",
keywords = "bone marrow, Cell therapy, mesenchymal stromal cell, multiple sclerosis",
author = "Juliana Redondo and Pamela Sarkar and Kevin Kemp and Virgo, {Paul F.} and Joya Pawade and Aimie Norton and Emery, {David C.} and Guttridge, {Martin G.} and Marks, {David I.} and Alastair Wilkins and Scolding, {Neil J.} and Rice, {Claire M.}",
year = "2018",
month = "6",
day = "1",
doi = "10.1177/1352458517711276",
language = "English",
volume = "24",
pages = "919--931",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "7",

}

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TY - JOUR

T1 - Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro

AU - Redondo, Juliana

AU - Sarkar, Pamela

AU - Kemp, Kevin

AU - Virgo, Paul F.

AU - Pawade, Joya

AU - Norton, Aimie

AU - Emery, David C.

AU - Guttridge, Martin G.

AU - Marks, David I.

AU - Wilkins, Alastair

AU - Scolding, Neil J.

AU - Rice, Claire M.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - bone marrow

KW - Cell therapy

KW - mesenchymal stromal cell

KW - multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=85038587525&partnerID=8YFLogxK

U2 - 10.1177/1352458517711276

DO - 10.1177/1352458517711276

M3 - Article

VL - 24

SP - 919

EP - 931

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

IS - 7

ER -