Age-related changes in rat bone-marrow mesenchymal stem cell plasticityReportar como inadecuado

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BMC Cell Biology

, 12:44

Cell differentiation and proliferation


BackgroundThe efficacy of adult stem cells is known to be compromised as a function of age. This therefore raises questions about the effectiveness of autologous cell therapy in elderly patients.

ResultsWe demonstrated that the expression profile of stemness markers was altered in BM-MSCs derived from old rats. BM-MSCs from young rats 4 months expressed Oct-4, Sox-2 and NANOG, but we failed to detect Sox-2 and NANOG in BM-MSCs from older animals 15 months. Chondrogenic, osteogenic and adipogenic potential is compromised in old BM-MSCs. Stimulation with a cocktail mixture of bone morphogenetic protein BMP-2, fibroblast growth factor FGF-2 and insulin-like growth factor IGF-1 induced cardiomyogenesis in young BM-MSCs but not old BM-MSCs. Significant differences in the expression of gap junction protein connexin-43 were observed between young and old BM-MSCs. Young and old BM-MSCs fused with neonatal ventricular cardiomyocytes in co-culture and expressed key cardiac transcription factors and structural proteins. Cells from old animals expressed significantly lower levels of VEGF, IGF, EGF, and G-CSF. Significantly higher levels of DNA double strand break marker γ-H2AX and diminished levels of telomerase activity were observed in old BM-MSCs.

ConclusionThe results suggest age related differences in the differentiation capacity of BM-MSCs. These changes may affect the efficacy of BM-MSCs for use in stem cell therapy.

List of AbbreviationsBM-MSCbone marrow-derived mesenchymal stem cells

BMP-2bone morphogenetic protein 2

BSAbovine serum albumin

cTnIcardiac troponin I

cTnTcardiac troponins T

cTnCcardiac troponin C: cTrpm: cardiac tropomyosin

DAPI4-: 6-diamidino-2-phenylindole

DMEM-HGDulbecco-s modified Eagle-s medium-high glucose

EGFepidermal growth factor

FACSfluorescence-activated cell sorting

FBSfetal bovine serum

FGF-2fibroblast growth factor 2

FITCfluorescein isothiocyanate

G-CSFgranulocyte colony stimulating factor

IGF-1insulin-like growth factor 1

NVCMneonatal ventricular cardiomyocytes

OBM-MSCold bone marrow mesenchymal stem cells

PBSphosphate buffered saline


TRITCtetramethylrhodamine isothiocyanate

VEGFvascular endothelial growth factor

YBM-MSCyoung bone marrow mesenchymal stem cells

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-12-44 contains supplementary material, which is available to authorized users.

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Autor: Faizal Z Asumda - P Bryant Chase


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