Yasushi Yoshikawa1, Shigeru Miyagawa1, Koichi Toda1, Atsuhiro Saito1, Yasushi Sakata2, Yoshiki Sawa3. 1. Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 (E1) Yamadaoka, Suita, Osaka, 565-0871, Japan. 2. Department of Cardiology, Osaka University Graduate School of Medicine, Osaka, Japan. 3. Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 (E1) Yamadaoka, Suita, Osaka, 565-0871, Japan. yoshikawa@surg1.med.osaka-u.ac.jp.
Abstract
BACKGROUND AND PURPOSE: Despite promising experimental results, clinically, intramyocardial myoblast injection failed to reverse remodeling and it induced arrhythmogenicity. In contrast, scaffold-free skeletal muscle-derived cell (SC) sheets attenuated cardiac dysfunction and arrhythmogenicity via paracrine effects. We report the first clinical trial of SC sheet implantation (SCSI) conducted in four patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD). METHODS: SC sheets were made from muscle fibers and multi-layered SC sheets were applied to the left ventricular (LV) anterolateral surface via left thoracotomy. RESULTS: There were no major cardiac adverse events. Ventricular arrhythmia decreased in all except one patient, in whom global LV function did not improve. The LV volume decreased and LV ejection fraction improved in all except the same patient. Systolic wall thickening, reflecting regional wall motion, improved in the sheet-implanted areas, and vessels in the LV apex increased in all patients, suggesting angiogenesis. The LVAD was successfully removed in two patients. CONCLUSIONS: SCSI induced reverse remodeling and angiogenesis, and improved LV function, allowing LVAD removal in two patients, although functional recovery failed to improve in the one non-responder, even with angiogenesis. SCSI is a promising regenerative therapy for DCM patients responsive to this strategy, even with LVAD assistance.
BACKGROUND AND PURPOSE: Despite promising experimental results, clinically, intramyocardial myoblast injection failed to reverse remodeling and it induced arrhythmogenicity. In contrast, scaffold-free skeletal muscle-derived cell (SC) sheets attenuated cardiac dysfunction and arrhythmogenicity via paracrine effects. We report the first clinical trial of SC sheet implantation (SCSI) conducted in four patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD). METHODS: SC sheets were made from muscle fibers and multi-layered SC sheets were applied to the left ventricular (LV) anterolateral surface via left thoracotomy. RESULTS: There were no major cardiac adverse events. Ventricular arrhythmia decreased in all except one patient, in whom global LV function did not improve. The LV volume decreased and LV ejection fraction improved in all except the same patient. Systolic wall thickening, reflecting regional wall motion, improved in the sheet-implanted areas, and vessels in the LV apex increased in all patients, suggesting angiogenesis. The LVAD was successfully removed in two patients. CONCLUSIONS: SCSI induced reverse remodeling and angiogenesis, and improved LV function, allowing LVAD removal in two patients, although functional recovery failed to improve in the one non-responder, even with angiogenesis. SCSI is a promising regenerative therapy for DCMpatients responsive to this strategy, even with LVAD assistance.
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