UNRAVEL FIBROBLAST EPITHELIAL CROSSTALK SUPPORTING KERATINOCYTES SELF-RENEWAL TO IMPROVE SKIN GRAFT PRODUCTION

Skin stem cells can be used to produce skin grafts for transplantation purposes. These regenerative therapies are life-saving procedures and have been demonstrated to be successful and safe for the treatment of burns and severe genetic diseases. Long lasting skin regeneration requires the correct amount of stem cells (SCs) in the graft. However, the treatment of large burns or skin replacement therapy in elderly patients are still challenging. In such conditions, the limited donor sites and the physiological reduction of SCs results in the insufficient availability of SCs for the graft production. A way to produce efficiently more SCs is to enforce their self-renewing – the process of generating more SCs – capacity. A condition that forces SCs to increase their self-renewal capacity is stretching. With this project, we will generate a comprehensive atlas of the changes occurring in space and time during tissue stretching. Based on this atlas, we will elucidate the signalling molecules instructing SCs self-renewal and we will identify modalities to target such molecules. This knowledge will be used to develop cell culture conditions to ameliorate skin graft productions for clinical application. Collectively, such insights will provide new fundamental knowledge on the biology of SCs and this approach will ameliorate the clinical success of skin regenerative and replacement therapies to the benefits of patients.