Korean J Transplant.  2022 Nov;36(Supple 1):S186. 10.4285/ATW2022.F-3118.

Application of engineered cell sheets composed of human islets and supporting stem cells enhances the outcome of islet cell transplantation in vitro and in vivo

• Yoshino K
• Adachi T
• Matsushima, H
• Imamura H
• Maruya Y
• Hara T
• Soyama A
• Hidaka M
• Eguchi S

• KMID: 2535702
• DOI: http://doi.org/10.4285/ATW2022.F-3118

Abstract

We have so far conducted various islet transplantation research using cell sheet engineering technique. By using engineered cell sheets composed of human islets and supporting cells, cytoprotective effect on islets and overcoming the issue of poor vascularization are expected. As a results, the improvement of the outcome of islet transplantation would be expected. In this study, we review our islet transplantation research to date and state future prospective. Engineered cell sheets composed of islets and mesenchymal stem cells (MSCs) derived from rats overcome the issue of poor vascularization in subcutaneous sites and succeeded in reversing DM in a rodent model. Co-culture of human islets with human fibroblast sheets showed higher viability rate with cytoprotective factors (VEGF and fibroblast growth factor) than islets-alone group. When fibroblasts, bone marrow-derived stem cells, and adipose-derived stem cells (ADSCs) respectively were co-cultured with islet cells, ADSCs were found to be beneficial in terms of viability and VEGF production. An engineered cell sheets composed of pig islets and ADSC sheets were transplanted subcutaneously into type I diabetic pig models. Subcutaneous transplantation of engineered islet/ADSC sheets could regulate the blood glucose levels even in large animal models. Application of engineered cell sheets composed of human islets and supporting cells, we have showed the cytoprotective effect on islets in vitroand achieved better glycemic control in vivo. ADSCs are considered as an attractive cell source for creating engineered cell sheets.