Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.
BACKGROUND
Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs.


RESULTS
Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation.


CONCLUSIONS
The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.
Wilson
Amber
A
Department of Molecular and Cellular Pharmacology, and the Vascular Biology Institute, University of Miami School of Medicine, Miami, FL 33136, USA.
Shehadeh
Lina A
LA
Yu
Hong
H
Webster
Keith A
KA
D000375:Aging; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D036341:Intercellular Signaling Peptides and Proteins