Abstract 17388: Autologous Cell-sheet Transplantation Therapy for Treating Cardiomyopathy: A Phase I Clinical Trial of Novel Stem Cell Therapy
Background: Transplantation of autologous somatic tissue-derived cells into the heart has been shown to yield functional recovery of the failing heart via “paracrine effects” that enhance the native regenerative process; however, the reported therapeutic effects are clinically modest. We have developed the cell-sheet method in which scaffold-free cell-sheets are attached on the epicardial surface to maximize the paracrine effects. Based upon the “proof-of-concept” studies, Phase I Clinical Trial was launched to test the hypothesis that autologous skeletal muscle-derived cell-sheets transplantation may be feasible, safe and effective for treating severe congestive heart failure.
Methods: First study enrolled 4 dilated cardiomyopathy (DCM) patients with LVAD. Second Study enrolled 7 DCM patients and 8 Ischemic cardiomyopathy patients (ICM) of NYHA functional class III or IV, who were already treated by maximum medical and/or interventional therapies. Scaffold-free cell-sheets containing 3-9х108 autologous muscle-derived cells were transplanted over the LV free wall via the left thoracotomy without additional interventional treatments.
Results: There was no procedure-related mortality or major complications in both study. In the First Study, 2 of 4 patients showed functional recovery and succeeded in bridge to recovery from LVAD. In second study, all patients were discharged from the hospital without mortalities over the follow-up (median 24 months). All patients insisted marked symptomatic improvement post-treatment evaluated by SAS. In addition, 6-minute walk test showed a significant improvement. Multi-slice CT scanning revealed that in ICM patients whose LVESVI was between 100 and 130 showed LV reverse remodeling 6 months after sheet implantation compared with pre-value. Survival rate was better after cell sheet implantation compared with estimated value calculated by the Seattle heart failure model.
Conclusions: In this Phase I study, cell-sheet transplantation as a sole therapy was feasible and safe for treating cardiomyopathy. Promising results in functional recovery warrant further clinical follow-up and accumulation of the cases to prove the therapeutic efficacy of this treatment for severe congestive heart failure.
- © 2013 by American Heart Association, Inc.