Advanced age impairs cardioprotective function of mesenchymal stem cell transplantation from patients to myocardially infarcted rats.

OBJECTIVES Mesenchymal stem cells (MSCs) have limited clinical therapeutic effects in older myocardial infarction (MI) patients. Thus, whether younger MSCs might confer greater protection is worth investigating. METHODS Human MSCs (hMSCs) were isolated before coronary artery bypass graft surgery and growth characteristics of hMSCs at passage 3 were observed. Vascular endothelial growth factor (VEGF) and Bcl-2 mRNA and protein expression from hMSCs were measured. In vivo, 45 adult male rats with MI were randomized to receive one of three treatments: old hMSCs, young hMSCs or culture medium (control) transplanted into infarcted myocardium. Echocardiography, TUNEL, immunohistochemistry and Western blot were used to assess results. RESULTS hMSC proliferation in the old group was significantly lower than the young group. VEGF decreased 35% and Bcl-2 decreased more than 60% at the mRNA level; VEGF and Bcl-2 protein were decreased in the old versus the young group. hMSC transplantation may improve cardiac function, but MSC source may affect therapeutic efficacy. Similar data were obtained from TUNEL, immunohistochemistry and Western blot. CONCLUSION Transplantation of hMSCs improves heart function, but proliferative ability and myocardial protection decrease with older MSCs, likely due to differences between VEGF and Bcl-2 expression and reduced anti-apoptosis.