Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium

Journal of Molecular and Cellular Cardiology
Shujia JiangMuhammad Ashraf

Abstract

Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young ((Yng)MSCs; 8-12 weeks) and old ((Old)MSCs; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by (Yng)MSCs under anoxia as compared to (Old)MSCs, cultured either alone or in co-culture ((Co-old)MSCs) with (Yng)MSCs. Likewise, (Yng)MSCs were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to (Old)MSCs and (Co-old)MSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n=38). The animals were grouped to receive 70 microl basal DMEM without cells (group 1) or containing 2 x 10(6)(Yng)MSCs (PKH67 labeled; group 2) or (Old)MSCs (PKH26 labeled; group 3) and mixture of (Yng)MSCs + (Old)MSCs (1 x 10(6) cells each; group 4). Histological studies...Continue Reading

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Citations

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Jul 19, 2014·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Xianbao LiuJian'an Wang
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