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J Thorac Cardiovasc Surg 1999;118:715-725
© 1999 Mosby, Inc.
CARDIOTHORACIC TRANSPLANTATION |
From the Division of Cardiovascular Surgery and The Center for Cardiovascular Research, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Address for reprints: Ren-Ke Li, MD, PhD, Toronto Hospital– General Division, CCRW 1-815, 101 College St, Toronto, Ontario, Canada, M5G 2C4.
Objective: We have previously reported that fetal cardiomyocyte transplantation into myocardial scar improves heart function. The mechanism by which this occurs, however, has not been elucidated. To investigate possible mechanisms by which cell transplantation may improve heart function, we compared cardiac function after transplantation of 3 different fetal cell types: cardiomyocytes, smooth muscle cells (nonstriated muscle cells), and fibroblasts (noncontractile cells).
Methods: A left ventricular scar was created by cryoinjury in adult rats. Four weeks after injury, cultured fetal ventricular cardiomyocytes (n = 13), enteric smooth muscle cells (n = 10), skin fibroblasts (n = 10), or culture medium (control, n = 15 total) were injected into the myocardial scar. All rats received cyclosporine A (INN: ciclosporin). Four weeks after transplantation, left ventricular function was evaluated in a Langendorff preparation.
Results: The implanted cells were identified histologically. All transplanted cell types formed tissue within the myocardial scar. At an end-diastolic volume of 0.2 mL, developed pressures in cardiomyocytes group were significantly greater than smooth muscle cells and skin fibroblasts groups (cardiomyocytes, 134% ± 22% of control; smooth muscle cells, 108% ± 14% of control; skin fibroblasts, 106% ± 17% of control; P = .0001), as were +dP/dtmax (cardiomyocytes, 119% ± 37% of control; smooth muscle cells, 98% ± 18% of control; skin fibroblasts, 92% ± 11% of control; P = .0001) and –dP/dtmax (cardiomyocytes, 126% ± 29% of control; smooth muscle cells, 108% ± 19% of control; skin fibroblasts, 99% ± 16% control; P = .0001).
Conclusions: Fetal cardiomyocytes transplanted into myocardial scar provided greater contractility and relaxation than fetal smooth muscle cells or fetal fibroblasts. The contractile and elastic properties of transplanted cells determine the degree of improvement in ventricular function achievable with cell transplantation.
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