Mesenchymal stem cells conditioned with glucose depletion augments their ability to repair‐infarcted myocardium

Mesenchymal stem cells ( MSC s) 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, MSC s 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 , p16 INK4a , p21 and p53 along with measurements of population doubling ( PD ), superoxide dismutase ( SOD ) activity and apoptosis. Aged MSC s 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 MSC s 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 MSC s, myocardial infarction ( MI ) was induced in 24 months old C57 BL /6 wild type mice and GFP expressing untreated and pre‐conditioned aged MSC s were transplanted. Hearts transplanted with pre‐conditioned aged MSC s 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 t max , d p /d t min , 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 MSC s with glucose depletion can enhance proliferation, delay senescence and restore the ability of aged cells to repair senescent infarcted myocardium.