Background-Autologous bone marrow cells (BMCs) transplanted into ventricula
r scar tissue may differentiate into cardiomyocytes and restore myocardial
function. This study evaluated cardiomyogenic differentiation of BMCs, thei
r 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 mu
mol/L), TGF beta 1 (10ng/mL), or insulin (1 nmol/L) (n=6, each group). Only
BMCs cultured with 5-aza formed myotubules which stained positively for tr
oponin 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, fre
sh BMCs (n=9), cultured BMCs (n=9), 5-aza-induced BMCs (n=12), and medium (
control, n=12) 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 observ
ed 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 (P<0.05) than that of the control hearts. All transplante
d BMCs induced angiogenesis in the scar.
Conclusions-Transplantation of BMCs induced an,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.