Adipose-derived Stem Cells Seeded In A Soft Collagen Hydrogel Improve Healing In Murine Burns
Janos Barrera, BS, Zeshaan N. Maan, MD, Dominik Duscher, MD, Alexander J. Whittam, BA, Marcelina Perez, BS, Revanth Kosaraju, N/A, Geoffrey C. Gurtner, MD, FACS.
Stanford School of Medicine, Stanford, CA, USA.
Post-burn scars and scar contractures have important functional and psychosocial implications for patients. Recently, stem cell therapy has gained attention as a potential therapeutic solution for this clinical challenge. Mesenchymal stem cells (MSCs) have been shown to stimulate angiogenesis, modulate inflammation, and improve wound healing. Our lab recently developed a soft collagen hydrogel that, when seeded with MSCs, improves MSC viability and augments their pro-regenerative capacity. Using a contact burn model in wild-type (WT) mice, we studied the effects of adipose-derived mesenchymal stem cell (ASC)-seeded hydrogels on wound healing following thermal injury.
Partial thickness contact burns were created on the dorsum of WT mice. On days 5 and 10 following injury, burns were debrided and received either ASC-hydrogel, ASC injection, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis.
ASC-hydrogel treated burns showed accelerated healing and time to re-epithelialization, compared with ASC injection, hydrogel-alone or control burns. ASC-hydrogel treated burns exhibited increased vascularity, along with increased expression of the pro-angiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the pro-fibrotic gene Timp1 and pro-inflammatory gene Tnfa were down-regulated in ASC-hydrogel treated burns. Furthermore, ASC-hydrogel treated burns exhibited reduced scar area compared to hydrogel-treated and control wounds, with equivalent scar density.
ASC-hydrogel therapy is effective for treating burns, with demonstrated pro-angiogenic, fibromodulatory and immunomodulatory effects. Further refinement and testing is indicated to facilitate clinical translation.
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