Effect of Rapamycin on mesenchymal stem cells treatment for swine myocardial infarction

Objectives: The aim of this study is to investigate the effect of Rapamycin on marrow mesenchymal stem cells (MSCs) transplantation in acute myocardial infarction in swine by means of detecting myocardial perfusion and glucose metabolism in global left ventricular myocardium, combined with assessment of cardiac function on SPECT, PET and MRI. The changes of glucose transporters, and the related signal transduction pathway which may participate in the MSCs paracrine process will be detected.

Methods: Eighteen Chinese mini-swine were randomized into 3 groups: Control group (n=6), MSCs transplantation group (MSCs group; n=6) and MSCs+Rapamycin group (Rapamycin group; n=6). The swine in the Rapamycin group received oral medication of Rapamycin per day. One month later, myocardial infarction was induced in swine hearts. The MSCs group and Rapamycin group received autologous MSCs transplantation through intramyocardial injection into the peri-infarcted areas, and the Control group were subjected to saline in the same way. After four weeks, myocardial perfusion, myocardial glucose metabolism and cardiac function were evaluated in the two groups through SPECT, PET-CT and MRI. On the end point, PCR and immunohistochemical staining were performed to detect the related genes and proteins.

Results: On SPECT, summed rest score (SRS), and Defect area (cm²) in the Rapamycin group are lower than Control group and MSCs group; On PET, SCR and Scar area (%) in the Rapamycin group are also lower than Control group and MSCs group. On MRI, there were no significant difference in EDV(ml) between the three groups, however, the ESV(ml) in the Rapamycin group are higher than the MSCs group, and the EF(%) value was lower than the other groups (Table.1). In PCR, there were significant differences in the three groups in GLUT4, mTOR and p70s6k (Fig.1).

Conclusions: Four weeks after MSCs transplantation for curing AMI, the myocardial perfusion and glucose metabolism improved significantly in the Rapamycin group; however, the cardiac function was decreased. It is speculated that Rapamycin might have impacted the effect of MSCs transplantation in infarcted hearts. The mechanism needs further research.

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