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Khan M, Mohsin S, Khan SN, Riazuddin S: Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. J Cell Mol Med. 2009 Dec 11.
ABSTRACT Myocardial infarction is one of the leading causes of mortality in aged people. Whether age of donors of mesenchymal stem cell (MSCs) affects its ability to repair the senescent heart tissue is unknown. In the present study, MSCs from young (2 months) and aged (18 months) GFP expressing C57BL/6 mice were characterized with p16 (INK4a) and beta-gal associated senescence. Myocardial infarction was produced in 18 month old wild type C57BL/6 mice transplanted with MSCs from young and aged animals in the border of the infarct region. Expression of p16 (INK4a) in MSCs from aged animals was significantly higher (21.5%+/- 1.2, p <0.05) as compared to those from young animals (9.2%+/- 2.8). A decline in the tube-forming ability on Matrigel was also observed in aged MSCs as well as down-regulation of IGF-1, FGF-2, VEGF and HGF compared to young cells. Mice transplanted with young MSCs exhibited significant improvement in their LV systolic and diastolic function as demonstrated by dp/dt (max), dp/dt (min), P (max). Reduction in the LV fibrotic area was concomitant with neovascularization as demonstrated by CD31 and SMA expression. Real time RT-PCR analysis for VEGF, SDF-1a and GATA-4 genes further confirmed the effect of age on MSC differentiation towards cardiac lineages and enhanced angiogenesis. These studies lead to the conclusion that repair potential of MSCs is dependent on the age of donors and the repair of senescent infarcted myocardium requires young healthy MSCs. |
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