Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.
Mult Scler
; 24(7): 919-931, 2018 06.
Article
de En
| MEDLINE
| ID: mdl-28548004
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 ß-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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Vieillissement de la cellule
/
Prolifération cellulaire
/
Cellules souches mésenchymateuses
/
Sclérose en plaques
Limites:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Mult Scler
Sujet du journal:
NEUROLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Royaume-Uni