Wharton’s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction

OBJECTIVE: To investigate the therapeutic effects of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) on myocardial regeneration and cardiac repair after acute myocardial infarction (AMI). MATERIALS AND METHODS: WJ-MSCs were isolated from human umbilical cord under sterile conditions and were cultured and expanded until passage 5. WJ-MSCs were labeled with CM-Dil before transplantation. The mid-third of the left anterior descending artery was ligated surgically to establish a mini-swine AMI model. The miniswines were divided randomly into three groups (n=6 in each): control group, PBS group, and transplantation group. Six weeks later, evaluation of the changes in myocardial perfusion and function was performed by single-photon emission computed tomography and echocardiography in each group. Then, the animals were euthanized and the tissues in the infarcted area were harvested for histopathological examination. RESULTS: The changes in myocardial perfusion and function were significantly improved in the transplantation group compared with the control and PBS groups (P<0.001). Immunofluorescence results confirmed that the transplanted WJ-MSCs were still alive and part of them appeared to have differentiated into cardiomyocytes and vascular endothelia 6 weeks after transplantation. In the meantime, it was also observed that resident cardiac stem cells also recruited and differentiated into neonatal cardiomyocytes and vascular endothelia. Masson's trichrome showed more viable myocardium and less fibrous tissue in the transplantation group compared with the other two groups (P<0.001). Vessel density was augmented and cell apoptosis was reduced in the transplantation group compared with the control and PBS groups (P<0.001). CONCLUSION: WJ-MSCs transplanted by a direct injection into the infarcted area could survive and differentiate into cardiomyocytes and endothelial cells. They also promoted recruitment and differentiation of cardiac stem cells in a porcine model with AMI. In addition, WJ-MSC transplantation reduced apoptosis and fibrosis, enhanced viable myocardium, and thus improved ventricular remodeling and function.