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BioMed Research International
Volume 2013 (2013), Article ID 583912, 6 pages
http://dx.doi.org/10.1155/2013/583912
Review Article

Present and Future Perspectives on Cell Sheet-Based Myocardial Regeneration Therapy

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine E1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Received 4 October 2013; Accepted 28 October 2013

Academic Editor: Ryuichi Morishita

Copyright © 2013 Yoshiki Sawa and Shigeru Miyagawa. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Heart failure is a life-threatening disorder worldwide and many papers reported about myocardial regeneration through surgical method induced by LVAD, cellular cardiomyoplasty (cell injection), tissue cardiomyoplasty (bioengineered cardiac graft implantation), in situ engineering (scaffold implantation), and LV restrictive devices. Some of these innovated technologies have been introduced to clinical settings. Especially, cell sheet technology has been developed and has already been introduced to clinical situation. As the first step in development of cell sheet, neonatal cardiomyocyte sheets were established and these sheets showed electrical and histological homogeneous heart-like tissue with contractile ability in vitro and worked as functional heart muscle which has electrical communication with recipient myocardium in small animal heart failure model. Next, as a preclinical study, noncontractile myoblast sheets have been established and these sheets have proved to secrete multiple cytokines such as HGF or VEGF in vitro study. Moreover, in vivo studies using large and small animal heart failure model have been done and myoblast sheets could improve diastolic and systolic performance by cytokine paracrine effect such as angiogenesis, antifibrosis, and stem cell migration. Recently evidenced by these preclinical results, clinical trials using autologous myoblast sheets have been started in ICM and DCM patients and some patients showed LV reverse remodelling, improved symptoms, and exercise tolerance. Recent works demonstrated that iPS cell-derived cardiomyocyte sheet were developed and showed electrical and microstructural homogeneity of heart tissue in vitro, leading to the establishment of proof of concept in small and large animal heart failure model.