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(Circulation. 2005;112:I-129 – I-134.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Administration of Control-Released Hepatocyte Growth Factor Enhances the Efficacy of Skeletal Myoblast Transplantation in Rat Infarcted Hearts by Greatly Increasing Both Quantity and Quality of the Graft

Keiichi Tambara, MD; Goditha U. Premaratne, MD; Genichi Sakaguchi, MD; Naoki Kanemitsu, MD; Xue Lin, MD; Hiroyuki Nakajima, MD; Yutaka Sakakibara, MD; Yu Kimura, BS; Masaya Yamamoto, PhD; Yasuhiko Tabata, PhD, DMedSci, Dpharm; Tadashi Ikeda, MD, PhD; Masashi Komeda, MD, PhD

From the Department of Cardiovascular Surgery, Graduate School of Medicine (K.T., G.U.P., G.S., N.K., X.L., H.N., Y.S., T.I., M.K.), and the Department of Biomaterials, Institute for Frontier Medical Sciences (Y.K., M.Y., Y.T.), Kyoto University, Kyoto, Japan.

Correspondence to Dr Masashi Komeda, Graduate School of Medicine, Department of Cardiovascular Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507. E-mail masakom{at}kuhp.kyoto-u.ac.jp

Background— We investigated whether simultaneous administration of control-released hepatocyte growth factor (HGF) enhances the efficacy of skeletal myoblast (SM) transplantation (Tx) through its antiapoptotic, angiogenic, and antifibrotic effects in myocardial infarction (MI).

Methods and Results— Forty-eight Lewis rats with chronic MI were divided into 4 groups. In Group I (n=14), neonatal SMs (5x10⁶) were transplanted in the MI area with a gelatin sheet incorporating 40 µg (1 g/L) of HGF applied. Group II (n=14) had SM Tx and placement of a saline sheet. Groups III (n=10) and IV (n=10) had culture medium injection plus HGF and saline sheet application, respectively. Four rats each from Groups I and II were sacrificed at day 1 for TUNEL assay on donor SMs. The percentage of TUNEL-positive donor cells was much lower in Group I than in Group II (P<0.05). At 4 weeks, in Group I, left ventricular diastolic dimension was smallest in echocardiography, end-systolic elastance was highest, and was the lowest (both P<0.0005 in ANOVA) in cardiac catheterization. Vascular density inside the graft was higher in Group I than in Group II (P<0.0001). The percentage of fibrotic area inside the graft was smaller in Group I than in Group II (P<0.001). The graft volume as estimated by fast skeletal myosin heavy chain-positive areas was 7-fold larger in Group I than in Group II (P<0.0001).

Conclusions— In SM Tx, HGF can greatly increase the graft volume and vascularity and reduce fibrosis inside the graft, which enhances the efficacy of SM Tx to infarcted hearts.

Key Words: apoptosis • cells • muscles • myocardial infarction • transplantation