316 Effects of Dsg2 antibodies on SCC tumor growth and survival

Abstract

Given the increasing aging population, the study and care of non-healing wounds in the elderly have become a priority for researchers and clinicians. Skin autografting can be the optimal approach to achieve complete healing of chronic wounds, and in vitro skin bioengineering has been explored to develop full-thickness skin equivalents for transplantation. However, available skin equivalents perform poorly during engraftment due to the lack of proper vasculature. Through advances in skin tissue engineering and induced pluripotent stem cell (iPSC) research, the quality and complexity of bioengineered skin equivalents may be significantly improved by inducing vascularization. In this study, we optimized approaches to derive endothelial cells (hiPSC-ECs) and keratinocytes (hiPSC-Ks) from human iPSCs and validated the contribution of these iPSC-derived cells into life-like 3D full thickness skin models using in vitro and in vivo assays. As a result, we established a vascularized skin graft equivalent through the co-culture of hiPSC-Ks and hiPSC-ECs with human fibroblasts in vitro. The incorporation of endothelial cells enhanced the reconstitution of human skin in an in vivo xenograft model. We are developing vascularized skin grafts solely from hiPSC-ECs, hiPSC-Ks and iPSC-derived fibroblasts. This study provides the foundation for using iPSCs to generate rejuvenated vascularized bioengineered skin equivalents to improve the long-term survival and functionality of skin grafts in elderly patients. This model will allow us to study the formation of the vasculature system and the dynamic interactions of skin fibroblasts and keratinocytes with vascular endothelial cells.