Objective: We have previously reported that fetal cardiomyocyte transplanta
tion into myocardial scar improves heart function. The mechanism by which t
his occurs, however, has not been elucidated. To investigate possible mecha
nisms by which cell transplantation may improve heart function, we compared
cardiac function after transplantation of 3 different fetal cell types: ca
rdiomyocytes, smooth muscle cells (nonstriated muscle cells), and fibroblas
ts (noncontractile cells). Methods: A left ventricular scar was created by
cryoinjury in adult rats. Four weeks after injury, cultured fetal ventricul
ar cardiomyocytes (n = 13), enteric smooth muscle cells (n = 10), skin fibr
oblasts (n = 10), or culture medium (control, n = 15 total) were injected i
nto the myocardial scar. All rats received cyclosporine A (INN: ciclosporin
), Four weeks after transplantation, left ventricular function was evaluate
d in a Langendorff preparation. Results: The implanted cells were identifie
d histologically, All transplanted cell types formed tissue within the myoc
ardial scar. At an end-diastolic volume of 0.2 mt, developed pressures in c
ardiomyocytes group were significantly greater than smooth muscle cells and
skin fibroblasts groups (cardiomyocytes, 134% +/- 22% of control; smooth m
uscle cells, 108% +/- 14% of control; skin fibroblasts, 106% +/- 17% of con
trol; P = .0001), as were +dP/dt(max) (cardiomyocytes, 119% +/- 37% of cont
rol; smooth muscle cells, 98% +/- 18% of control; skin fibroblasts, 92% +/-
11% of control; P = .0001) and -dP/dt(max) (cardiomyocytes, 126% +/- 29% o
f control; smooth muscle cells, 108% +/- 19% of control; skin fibroblasts,
99% +/- 16% control; P = .0001), Conclusions: Fetal cardiomyocytes transpla
nted into myocardial scar provided greater contractility and relaxation tha
n fetal smooth muscle cells or fetal fibroblasts, The contractile and elast
ic properties of transplanted cells determine the degree of improvement in
ventricular function achievable with cell transplantation.