Biomimetic Adipiose Stem Cell Dressing For Skin Regeneration
Artem Trotsyuk, Clark A. Bonham, Melanie Rodrigues, Paul Mittermiller, Jayakumar Rajadas, Mohammed Inayathullah, Geoffrey Gurtner.
Stanford University, Stanford University, CA, USA.
Background: Burns have important functional and psychosocial implications for patients. Decades of wound healing research have demonstrated a critical window within the first 24 hours after wounding during which there is a “switch” from scarless wound healing to scarring. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scar formation in burn wounds. Here, we identify an optimal stem cell population to stimulate angiogenesis, modulate inflammation and improve wound healing. We then optimize a delivery platform for the identified stem cell population and test the efficacy in a murine contact burn model.
Methods: Commercially-available and primarily isolated stem and progenitor cell populations were evaluated at a single cell level to determine which of the cells most closely resembled a fetal gene expression signature. Microfluidic single-cell qPCR and advanced bioinformatics was used to identify a potent subpopulation adipose-derived stromal cells (ASCs) that is found in both human and murine samples (CD26+/CD55+). Next, a hydrogel microenvironment was optimized for the identified ASC subpopulation. Finally, the cell-hydrogel combination was validated in a pre-clinical setting.
Results: Single-cell gene transcriptional analysis of cultured ASCs demonstrated a considerable increase the genes favorable to wound healing. Cells seeded with dual-capillary force on the pullulan-collagen hydrogel exhibited improved viability. Wounds treated with CD26+/CD55+ cells on a pullulan-collagen hydrogel showed improved wound healing and neovascularization in a murine contact burn model. These results suggest the regenerative potential of the identified ASC subpopulation for future clinical application.
Conclusion: The Gurtner laboratory has developed an ASC-hydrogel therapy for treating burns, with demonstrated pro-angiogenic, fibromodulatory and immunomodulatory effects. Further work is being done to validate the cell-hydrogel combination in a pre-clinical setting.
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