Impaired cardioprotective function of transplantation of mesenchymal stem cells from patients with diabetes mellitus to rats with experimentally induced myocardial infarction

Background: Diabetes mellitus (DM) exacerbates coronary artery disease (CAD) morbidity and mortality. Mesenchymal stem cells (MSCs) play an important therapeutic role in myocardial ischemic injury. However, little is known about changes in the cardioprotective characteristics of MSCs from patients with DM. Methods: Sternal bone marrow aspirates were taken at the time of coronary artery bypass graft surgery. The morphology and growth characteristics of hMSCs were observed in passage 3. Differences in gene expression profiling were measured by Affymetrix GeneChipHuman Genome U133 Plus 2.0 Arrays. Forty two adult male rats with experimentally CAD were randomized into three groups. MSCs from patients with CAD+DM or CAD were injected into the infarcted myocardium. Control animals received culture medium. Echocardiography, TUNEL, immunohistochemistry and Western-blot analysis were performed 4 weeks after transplantation. Results: Growth curves showed that proliferation of hMSCs in the CAD+DM group was significantly lower than in the CAD group. Nine transcripts of genes related to apoptosis containing Bcl-2 were found to differentiate the two groups. Transplantation of hMSCs in the infarcted border zone improved cardiac function, but DM partly impaired this effect. Similar results were observed from TUNEL, immunohistochemistry and Western-blot analysis. Conclusions: hMSCs from patients with CAD+DM and CAD alone both have proliferative properties. Transplantation of hMSCs ameliorate heart function, but proliferative ability and myocardial protection decrease significantly in MSCs obtained from patients with CAD+DM compared with cultures from patients with CAD alone, possibly as a result of differences in Bcl-2 protein expression and reduced anti-apoptosis.