499 A novel preclinical model for translating an induced pluripotent stem cell therapy for the treatment of skin diseases

Induced pluripotent stem cells (iPSCs) hold promise for treating recessive dystrophic epidermolysis bullosa (RDEB). An iPSC-based therapy RDEB involves multiple steps such as reprogramming, gene correction, iPSC differentiation, and transplantation of genetically corrected iPSC-derived skin onto patients. Strong evidence supports the use epidermal sheets or composite grafts final therapeutic products cells. However, generation is a lengthy consequently expensive process. To develop more straightforward cost effective approach, we established novel preclinical model grafting human cell suspension immunocompromised mice that requires low starting numbers. The silicone chamber sequential fibroblasts followed by keratinocytes. Both keratinocytes are delivered in fibrin-based gel formulation. Using this modified assay, have successfully engrafted 5 x 105 per 1.4 cm2 wound area. We also In all cases, grafted formed multilayered stratified epidermis. currently investigating strategies to deliver cells, including harvesting application techniques used Spray-On-Skin™ developed AVITA Medical. This approach will decrease time patient vs. it takes grow potentially simplify therapies other diseases.