Joint poster with I-STEM on “Regenerative and Immunocompatible hESC-Derived Skin Substitute for Sickle Cell Leg Ulcers” presented by Jean-François Bisson at the European Tissue Repair Society (ETRS) meeting in Rouen (France) in September 2026.
Authors: Sophie Domingues1,2, Annabelle Darle1,2, Houda Abla1,2, Imene Guiliano1,2, Jean-François Bisson3, Sara Abbas1,2, Patricia Senet4, Marc Peschanski1,2, Christine Baldeschi1,5
Affiliations:
- 1 Institut des cellules Souches pour le Traitement et l’Étude des maladies Monogéniques (I-STEM), 91100 Corbeil-Essonnes, France
- 2 Centre d’Etude des Cellules Souches, 91100 Corbeil-Essonnes, France
- 3 ETAP-LAB, 54500 Vandoeuvre-lès-Nancy, France
- 4 AH-HP, Groupe hospitalier Sorbonne-Université, 75 970 Paris, France
- 5 Université Paris-Saclay, U861, 91100 Corbeil-Essonnes, France
Abstract:
Sickle cell leg ulcers are chronic wounds that are difficult to heal and represent a major healthcare challenge due to limited treatments and increasing patient numbers. Novel tissue-based therapies are urgently needed. Advances in skin engineering have enabled substitutes manufactured under Good Manufacturing Practices (GMP) using adult stem cells such as keratinocytes. Human embryonic stem cells (hESC) also provide an unlimited source of differentiated cells for regenerative medicine.
We developed an Innovative Medicinal Product (IMP) composed of hESC-derived keratinocytes seeded on fibrin matrix to reconstruct a skin substitute produced in a dedicated medical device for manufacturing, transport, and clinical application. The GMP protocol enabled robust large-scale production of keratinocytes from GMP-grade hESC. The fibrin scaffold was generated from viro-inactivated pooled human plasma free of anti-HLA antibodies. Quality controls ensured identity, purity, potency, genomic stability, and safety of the IMP.
In vitro, the IMP formed a homogeneous epidermal-like layer expressing keratinocyte markers without pluripotency markers. Conditioned medium from the IMP significantly accelerated wound closure compared with fibrin alone. Cytokine profiling revealed enrichment in factors involved in wound healing, angiogenesis, and tissue repair.
In vivo, in nude mice, the IMP showed efficient engraftment and formed an epidermis expressing human markers, consistent with enhanced wound closure observed with conditioned medium versus fibrin alone. In addition, the product remained stable up to 96 hours after release, supporting its transport and clinical use.
In a humanized mouse model, the IMP showed no immune rejection and sustained graft survival, whereas primary cell-based constructs showed rejection. Biodistribution and toxicology studies showed no cell dissemination or toxicity six months after grafting.
Overall, these data demonstrate that a GMP-manufactured hESC-derived skin substitute is functional, bioactive, safe, and immunologically compatible in vivo. A first clinical trial is planned for early 2027.
