Green Fluorescent Protein-Transgenic Rat as a Tool for Study of Transplantation and Regeneration in Myocardium

Cell transplantation and regeneration therapy are potentially new therapeutic approaches for cardiovascular disease. Transgenic (tg) animals for reporter genes would be useful to follow the cell lineage and differentiation during development and regeneration processes. In the present study, we developed green fluorescent protein (GFP)-tg rats and evaluated them as a tool for the study of cardiomyocyte transplantation and regeneration. The myocardium and bone marrow cells derived from GFP-tg rats strongly expressed GFP. Because neonatal rat cultured cardiomyocytes also strongly expressed GFP, we transplanted GFP-tg rat-derived cardiomyocytes in a rat myocardial infarction (MI) model. Survival of GFP-tg rat-derived cardiomyocytes was confirmed. We further investigated whether bone marrow cells could differentiate into cardiomyocytes using this GFP-tg rat-derived bone marrow cells in vitro and in vivo. GFP-tg rat-derived bone marrow cells differentiated into cardiomyocyte- like cells (cardiac troponin I-expressed cells) by co-culture with wild rat cultured cardiomyocytes in vitro. Furthermore, differentiation of bone marrow cells into cardiomyocyte-like cells was observed by injection of GFP-tg rat-derived bone marrow cells in a rat MI model in vivo. These findings suggest that GFP-tg rats are a useful and valuable tool for the study of transplantation and regeneration in myocardium.