Abstract
BackgroundEpidermal grafting using cells derived from pluripotent stem cells will change the face of this side of regenerative cutaneous medicine. To date, the safety of the graft would be the major unmet deal in order to implement long-term skin grafting. In this context, experiments on large animals appear unavoidable to assess this question and possible rejection. Cellular tools for large animal models should be constructed.MethodsIn this study, we generated monkey pluripotent stem cell-derived keratinocytes and evaluated their capacities to reconstruct an epidermis, in vitro as well as in vivo.ResultsMonkey pluripotent stem cells were differentiated efficiently into keratinocytes able to reconstruct fully epidermis presenting a low level of major histocompatibility complex class-I antigens, opening the way for autologous or allogeneic epidermal long-term grafting.ConclusionsFunctional keratinocytes generated from nonhuman primate embryonic stem cells and induced pluripotent stem cells reproduce an in-vitro and in-vivo stratified epidermis. These monkey skin grafts will be considered to model autologous or allogeneic epidermal grafting using either embryonic stem cells or induced pluripotent stem cells. This graft model will allow us to further investigate the safety, efficacy and immunogenicity of nonhuman primate PSC-derived epidermis in the perspective of human skin cell therapy.
Highlights
Epidermal grafting using cells derived from pluripotent stem cells will change the face of this side of regenerative cutaneous medicine
Pluripotent stem cell (PSC) were seeded on mitomycin C-treated mouse embryonic fibroblast (MC-MEF) in Embryonic stem cell (ESC) medium (ESM; DMEM/F12 supplemented with 20% KO serum replacement, 1% nonessential amino acid, and 10 ng/ml basic Fibroblast growth factor (FGF) (Peprotech®))
The medium was replaced with FAD medium, as described by Guenou et al [2], supplemented with retinoic acid (RA) (1 μM; Sigma Aldrich®) and Bone morphogenic protein (BMP4) (0.05 nM; Peprotech®) during 6 days for monkey cells and with defined-Keratinocyte serum free medium (KSFM)® (ThermoFisher Scientific) supplemented with RA (1 μM) and BMP4 (0.5 nM) during 4 days for human cells
Summary
Epidermal grafting using cells derived from pluripotent stem cells will change the face of this side of regenerative cutaneous medicine. The safety of the graft would be the major unmet deal in order to implement long-term skin grafting. In this context, experiments on large animals appear unavoidable to assess this question and possible rejection. Preclinical models for regenerative medicine require the use of large animals possessing similar physiology and immunological response to human. In this context, nonhuman primates have a unique role in translational preclinical studies using pluripotent stem cell derivatives. The present study concerns the first development of nonhuman primate pluripotent stem cell-derived reconstructed epidermis that opens new perspectives to evaluate the efficacy and safety of skin graft in preclinical studies
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