Translational Research of iPS Cell Sheet-Based Myocardial Regeneration Therapy

Abstract

LVAD implantation and Heart transplantation have been well accepted as the ultimate lifesaving means of supporting end-staged heart failure patients. However, due to the limited durability of the LVAD and the shortage of donors, there are some limitations in these procedures. In this clinical situation, we developed cell sheet technology experimentally and introduced this to the treatment of severely damaged myocardium in clinical setting as translational research. In a series of pre-clinical experiments using animal heart failure model, we proved that myoblast sheets could heal the impaired heart mainly by cytokine paracrine effect. Evidenced by pre-clinical experiments, we applied myoblast sheets to 4 DCM patient receiving LVAD and 2 patients showed the recovery from LVAD. Although we implanted myoblast sheet to 20 heart failure patients without LVAD and some patients showed LV reverse remodeling. Recently we have developed human iPS cell derived cardiomyocyte sheet and obtained Proof of Concept by using porcine myocardial infarction model as preclinical study. And we have proved synchronous movement with recipient myocardium in vivo study. And also we have established large culture system and checked safety of iPS cell derived cardiomyocyte sheets for the purpose of clinical trial. iPS cell derived cardiomyocyte sheet may open new era in the treatment of severely damaged myocardium.