Wound Healing Society

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Allogeneic Cd26 / Cd55 Cell Therapy For Treating Burn Wounds
Artem Trotsyuk, Melanie Rodrigues, Clark Bonham, Paul Mittermiller, Geoffrey Gurtner.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, 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. Adipose-derived stromal cells (ASCs) have become increasingly useful for cell-based therapies due to the relative ease of extraction and demonstrated performance to stimulate angiogenesis, modulate inflammation and improve wound healing.
METHODS: We have identified a stem cell population both in mice and humans with an improved wound healing profile [Rennert et al. Nat Comm 2016]. Single cell analysis and fluorescence-activated cell sorting were used to identify and then isolate this novel ASC subpopulation with high precision by evaluating for CD45-, CD34+, CD26+ and CD55+ cells. The murine ASC subpopulation was expanded in culture and then seeded by dual capillary seeding onto a biocompatible pullulan-collagen hydrogel. The stem cell dressing was subsequently tested on a murine contact burn model in C57Bl/6 mice to measure the regenerative capabilities of the CD26+/CD55+ ASCs.
RESULTS: Wounds treated with CD26+/CD55+ cells demonstrated accelerated healing and time to re-epithelialization, brought about by increased VEGF and SDF1 expression and significantly higher neovascularization and collagen deposition (p<0.05). We also observed an increase in the expression of pro-angiogenic genes MCP-1, VEGF, and SDF-1 at both the protein and mRNA level (p<0.05). Expression of pro-fibrotic and pro-inflammatory genes was downregulated. On average, CD26+/CD55+ ASC treated wounds closed 4 days earlier when compared to the stromal vascular fraction and ASCs. Furthermore, ASC-hydrogel treated burns exhibited reduced scar area when compared to the untreated control.
CONCLUSION: We have developed an ASC-hydrogel therapy for treating burns, with demonstrated pro-angiogenic, fibromodulatory and immunomodulatory effects. We plan to further evaluate the efficacy of CD26+/CD55+ cells in a large animal model.


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