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Mesenchymal stem cells ( MSCs) are an attractive candidate for autologous cell therapy, but their ability to repair damaged myocardium is severely compromised with advanced age. Development of viable autologous cell therapy for treatment of heart failure in the elderly requires the need to address MSC ageing. In this study, MSCs from young (2 months) and aged (24 months) C57 BL/6 mice were characterized for gene expression of IGF-1 , FGF-2 , VEGF , SIRT-1 , AKT , p16INK4a , p21 and p53 along with measurements of population doubling ( PD), superoxide dismutase ( SOD) activity and apoptosis. Aged MSCs displayed senescent features compared with cells isolated from young animals and therefore were pre-conditioned with glucose depletion to enhance age affected function. Pre-conditioning of aged MSCs led to an increase in expression of IGF-1 , AKT and SIRT-1 concomitant with enhanced viability, proliferation and delayed senescence. To determine the myocardial repair capability of pre-conditioned aged MSCs, myocardial infarction ( MI) was induced in 24 months old C57 BL/6 wild type mice and GFP expressing untreated and pre-conditioned aged MSCs were transplanted. Hearts transplanted with pre-conditioned aged MSCs showed increased expression of paracrine factors, such as IGF-1 , FGF-2 , VEGF and SDF-1α. This was associated with significantly improved cardiac performance as measured by d p/d tmax, d p/d tmin, LVEDP and LVDP, declined left ventricle ( LV) fibrosis and apoptosis as measured by Masson's Trichrome and TUNEL assays, respectively, after 30 days of transplantation. In conclusion, pre-conditioning of aged MSCs with glucose depletion can enhance proliferation, delay senescence and restore the ability of aged cells to repair senescent infarcted myocardium. [ABSTRACT FROM AUTHOR]

Myocardial infarction is one of the leading causes of mortality in aged people. Whether age of donors of mesenchymal stem cells (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) green fluorescent protein expressing C57BL/6 mice were characterized with p16 [ABSTRACT FROM AUTHOR]

Abstract: Stem cell capability enhanced with cytokine administration is a promising treatment for myocardial infarction. Bone marrow stem cells (BMSCs) were isolated from C57BL/6 mice (8–12 weeks old) expressing GFP and characterized with c-kit and CD34. Infarcted heart tissue fragments were placed into dishes with BMSCs and medium supplemented with G-CSF, SCF, IGF-1 or combinations thereof were given to the BMSC-infarcted myocardium in vitro model. The IGF-1–G-CSF group showed significantly higher migration (67.7% ± 2.6) of c-kit+ BMSCs towards the ischemic tissue and expressed MEF-2 (43.7% ± 1.7). Of the single treatment groups, the G-CSF group demonstrated significantly higher migration of c-kit+ BMSCs (60.5 ± 2.7) with MEF-2 expression (38.7 ± 1.4). IGF-1 complements G-CSF and was relatively more significant in its effects on BMSC migration and cardiac lineage commitment towards ischemic heart tissue. [Copyright &y& Elsevier]