Abstract 12238: First Human Trial of Tissue-Engineered Skeletal Muscle-Derived Cell Sheet Implantation in Patients with Dilated Cardiomyopathy Supported by Left Ventricular Assist Device
Background: Despite promising experimental results, a clinical study found that intramyocardial myoblast injection failed to reverse LV remodeling and induced arrhythmogenicity. In contrast, we showed that scaffold-free skeletal muscle-derived cell sheets (SCSs) attenuated cardiac dysfunction and caused no arrhythmia through paracrine effects. Herein, we report results of the first clinical trial of SCS implantation in patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD), and discuss efficacy as well as safety and feasibility.
Methods and Results: Muscle specimens were collected from the Vastus Medialis. Cells obtained from muscle fibers [average, 6.1x108, 70% CD56(+) cells] were seeded in temperature-responsive dishes and cell sheets were collected without use of proteolytic enzymes. VEGF, HGF, and PDGF were recognized in the supernatants. Four-layered cell sheets were used to fully cover the LV anterolateral (AL) surface via a left thoracotomy. There were no major cardiac adverse events or life-threatening arrhythmia. Holter ECG showed that premature ventricular (PVC) arrhythmias were decreased, except in Case 2, in whom global LV function was not improved. In MDCT findings, LV volume decreased and LVEF was improved, except in Case 2. Systolic wall thickening (SWT), reflecting regional wall motion, was improved in the sheet-implanted area in all patients. CD31(+) cells in the LV apex myocardium were increased from 602±113 to 1003±113/mm2 (p=0.04), suggesting angiogenesis. The LVAD was successfully removed in Cases 1, 3, and 4, though case 4 required reuse of an LVAD 2 weeks later.
Conclusion: SCS induced a reverse remodeling effect, and improved global and regional LV functions as well as angiogenesis, which led to LVAD removal in 2 cases, while even a non-responder to SCS showed regional functional improvement. SCS implantation may be a promising regenerative therapy for DCM patients even with LVAD assistance.
- © 2011 by American Heart Association, Inc.