Shirasaka Tomonori, Miyagawa Shigeru, Fukushima Satsuki, Kawaguchi Naomasa, Nakatani Satoshi, Daimon Takashi, Okita Yutaka, Sawa Yoshiki
1 Division of Cardiovascular Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 2 Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan. 3 Department of Molecular Pathology, Graduate School of Medicine and Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan. 4 Division of Functional Diagnostics, Department of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan. 5 Division of Biostatistics, Hyogo College of Medicine, Hyogo, Japan.
Transplantation. 2016 Feb;100(2):295-302. doi: 10.1097/TP.0000000000001014.
Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart.
We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5).
Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010).
The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart.