Background-Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function. Methods and Results-In vitro studies: BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 mol/L), TGF␤1 (10ng/mL), or insulin (1 nmol/L) (nϭ6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (nϭ9), cultured BMCs (nϭ9), 5-aza-induced BMCs (nϭ12), and medium (control, nϭ12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza-treated BMC transplanted hearts had systolic and developed pressures which were higher (PϽ0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar. Conclusions-Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function. (Circulation. 1999;100[suppl II]:II-247-II-256.

5-Azacytidine-treated bone marrow stromal cells transplanted into the myocardial infarct region formed islands of cardiac-like tissue, induced angiogenesis, prevented thinning and dilatation of the infarct region, and improved regional and global contractile function.

Direct cell-cell interaction with cardiomyocytes was important for bone marrow stromal cells to differentiate into cardiomyocytes. This coculture was useful for simulating the cardiac environment in vitro for the research of cell transplantation in the heart.