Adipose-derived mesenchymal stem cells (ASCs) are well known for their secretory potential, which confers them useful properties in cell therapy. Nevertheless, this therapeutic potential is reduced after transplantation due to their short survival in the human body and their migration property. This study proposes a method to protect cells during and after injection by encapsulation in microparticles of calcium alginate. Besides, the consequences of encapsulation on ASC proliferation, pluripotential, and secretome were studied. Spherical particles with a mean diameter of 500 µm could be obtained in a reproducible manner with a viability of 70% after 16 days in vitro. Moreover, encapsulation did not alter the proliferative properties of ASCs upon return to culture nor their differentiation potential in adipocytes, chondrocytes, and osteocytes. Concerning their secretome, encapsulated ASCs consistently produced greater amounts of interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared to monolayer cultures. Encapsulation therefore appears to enrich the secretome with transforming growth factor β1 (TGF-β1) and macrophage inflammatory protein-1β (MIP-1β) not detectable in monolayer cultures. Alginate microparticles seem sufficiently porous to allow diffusion of the cytokines of interest. With all these cytokines playing an important role in wound healing, it appears relevant to investigate the impact of using encapsulated ASCs on the wound healing process.
Second-degree burns result in the loss of the epidermal barrier and could lead to delayed complications during the healing process. Currently, therapeutic options to treat severe burns are limited. Thus, this work aims to evaluate the effect of NaHS, a hydrogen sulfide (H2S) donor, in poloxamer hydrogel in topical application and the potentiating effect of injected encapsulated adipose-derived stem cells (ASCs) compared to monolayer ASCs using our previous second-degree burn model on human skin explants. Indeed, our model allows testing treatments in conditions similar to a clinical application. The observed benefits of NaHS may include an antioxidant role, which might be beneficial in the case of burns. Concerning ASCs, their interest in wound healing is more than well documented. In order to evaluate the efficiency of our treatments, we analyzed the kinetics of wound closure, keratinocyte proliferation, and dermal remodeling. The effect of NaHS led to a delay in re-epithelialization, with a decrease in the number of proliferating cells and a decrease in the synthesis of procollagen III. On the contrary, intradermal injection of ASCs, encapsulated or not, improves wound healing by accelerating re-epithelialization and collagen I synthesis; however, only encapsulated ASCs accelerate keratinocyte migration and increase the rate of procollagen III and collagen III. In conclusion, NaHS treatment did not improve burn healing. However, the injection of ASCs stimulated wound healing, which is encouraging for their therapeutical use in burn treatment.
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