Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro
Sophie Domingues, Annabelle Darle, Yolande Masson, Manoubia Saidani, Emilie Lagoutte, Ana Bejanariu, Julien Coutier, Raif Eren Ayata, Marielle Bouschbacher, Marc Peschanski, Gilles Lemaitre, Christine Baldeschi
Centre d’Etude des Cellules Souches, Corbeil-Essonnes; URGO RID, Chenôve; 3INSERM U861, I-Stem, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Corbeil-Essonnes
Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as a consequence of a prolonged inflammatory phase during the healing process. They are extremely hard to heal and persist as a significant health care problem due to the absence of effective treatment and the uprising number of patients. Indeed, there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds. Development in skin engineering leads to a small catalogue of available substitutes manufactured in Good Manufacturing Practices compliant (GMPc) conditions. Those substitutes are produced using primary cells that could limit their use due to restricted sourcing. Here, we propose GMPc protocols to produce functional populations of keratinocytes and fibroblasts derived from pluripotent stem cells to reconstruct the associated dermo-epidermal substitute with plasma-based fibrin matrix. In addition, this manufactured composite skin is biologically active and enhances in vitro wounding of keratinocytes. The proposed composite skin opens new perspectives for skin replacement using allogeneic substitute.
Keratinocyte Differentiation and Culture from stem cells, Fibroblast Differentiation and Culture from stem cells, and 3D cell culture,.
iPSC and ECS derived keratinocytes and fibroblasts