Journal de recherche et de thérapie sur les cellules souches

Abstrait

Promising Therapeutic Effects of Cell Sheet Implantation with a Pedicle Omentum Flap to Enhance the Angiogenic Response to Ischemic Cardiomyopathy

Yasuhiro Shudo, Shigeru Miyagawa, Satsuki Fukushima, Satoshi Kainuma, Atsuhiro Saito, Koichi Toda, Hiroyuki Nishi, Yasushi Yoshikawa, Akima Harada, Toshihiko Asanuma, Satoshi Nakatani, Tatsuya Shimizu, Teruo Okano and Yoshiki Sawa

Introduction: We previously reported that skeletal myoblast (SMB) sheets induced the functional recovery of distressed myocardium in a large or small animal heart failure model via the paracrine effect of cytokines; however, this method was limited by poor vascular network and cell retention. We hypothesized that wrapping the cell sheet with pedicle omentum—a well-vascularized organ delivering different stem cell types and releasing various angiogenic and anti-inflammatory factors—might support retention of the implanted cells and enhance the therapeutic effects of the cell sheet technique on ischemic cardiomyopathy (ICM). Methods and results: The ICM model was generated by inducing anterior myocardial infarction for 4 weeks in mini-pigs; whereas the scaffold-free cell sheets were generated from autologous SMBs in vitro. The cell sheets were placed on the infarct area with or without pedicle omentum wrapping. Mini-pigs that received the omentum flap only or no treatment were used as controls. The quantity of ironoxide-labeled transplanted cells was significantly greater with omentum wrapping than without at 8 weeks after treatment (60 ± 9% vs. 32 ± 4%) as determined by magnetic resonance imaging. Implantation of the cell sheet wrapped with omentum significantly improved the left ventricle systolic function, increased blood perfusion, and accelerated therapeutic vessel growth into the host ischemic myocardium. The inflammatory effect was more attenuated following implantation of the cell sheet wrapped with omentum. Conclusions: Use of the SMB cell sheet wrapped with pedicle omentum flap enhanced cell retention and promoted mature and functional microvasculature in porcine ICM model, thereby improving myocardial function.