Imaging the survival and utility of pre-differentiated allogeneic MSC in ischemic heart

The aim of the study is to track the survival and utility of mesenchymal stem cells (MSCs) and pre-differentiated MSCs in allogeneic infarcted myocardium. MSCs labeled with green fluorescent protein and luciferase (GFP-Fluc) were characterized by flow cytometry and multi-differentiation. 5-Azacytidine (5-AZ) was employed to induced cardiac differentiation from MSCs. Cardiac markers and immune antigen expression were assessed. Then, pre-differentiated MSCs induced by 5-AZ were intramyocardially injected into allogeneic C57 mice of myocardial infarction, undifferentiated MSCs were transplanted as control. The survival of transplanted cells, immune response and cardiac function of recipients were assessed with bioluminescence imaging, immunohistochemistry and echocardiography, respectively. In vitro results showed that 5-AZ treatment induced cardiac differentiation from MSCs, which also increased their expression of MHC-Ia and MHC-II. After intramyocardial transplantation in allogeneic mice, 5-AZ treated MSCs would rapidly be recognized and excluded by recipients. Meanwhile, a severe infiltration of immune cells could be detected. Though beneficial effects on cardiac function by 5-AZ treated MSCs could be detected, it was short and disappeared within 1 month. In contrast, undifferentiated MSCs were immune-privileged and could survive in allogeneic myocardium for more than 1 month, resulting in a significant improvement on cardiac function.