TY - JOUR
T1 - 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
AU - Tambara, Keiichi
AU - Premaratne, Goditha U.
AU - Sakaguchi, Genichi
AU - Kanemitsu, Naoki
AU - Lin, Xue
AU - Nakajima, Hiroyuki
AU - Sakakibara, Yutaka
AU - Kimura, Yu
AU - Yamamoto, Masaya
AU - Tabata, Yasuhiko
AU - Ikeda, Tadashi
AU - Komeda, Masashi
PY - 2005/8/30
Y1 - 2005/8/30
N2 - 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 (5 × 106) 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 τ 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.
AB - 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 (5 × 106) 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 τ 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.
KW - Apoptosis
KW - Cells
KW - Muscles
KW - Myocardial infarction
KW - Transplantation
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U2 - 10.1161/CIRCULATIONAHA.104.526293
DO - 10.1161/CIRCULATIONAHA.104.526293
M3 - Article
C2 - 16159804
AN - SCOPUS:24644520998
VL - 112
SP - I129-I134
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 9 SUPPL.
ER -