Adipose-Derived Stromal Cells Seeded in Pullulan-Collagen Hydrogels Improve Healing in Murine Burns

作者：Janos A. Barrera, Artem A. Trotsyuk, Zeshaan N. Maan, Clark Andrew Bonham, Madelyn R. Larson, Paul A. Mittermiller, Dominic Henn, Kellen Chen, Chyna J. Mays, Smiti Mittal, Alana M. Mermin-Bunnell, Dharshan Sivaraj, Serena L. Jing, Mélanie Rodrigues, Sun Hyung Kwon, Chikage Noishiki, Jagannath Padmanabhan, Yuanwen Jiang, Simiao Niu, Mohammed Inayathullah, Jayakumar Rajadas, Michael Januszyk, Geoffrey C. Gurtner · 发表于：Tissue Engineering Part A · 年份：2021 · DOI：10.1089/ten.tea.2020.0320 · 被引用次数：56 · 研究领域：Wound Healing and Treatments、Mesenchymal stem cell research、Burn Injury Management and Outcomes

Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known proangiogenic and immunomodulatory paracrine effects. Our laboratory has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their proangiogenic capacity in vivo. Concurrently, recent research suggests that prospective isolation of cell subpopulations with desirable transcriptional profiles can be used to further improve cell-based therapies. In this study, we examined whether adipose-derived stem cell (ASC)-seeded hydrogels could improve wound healing following thermal injury using a murine contact burn model. Partial thickness contact burns were created on the dorsum of mice. On days 5 and 10 following injury, burns were debrided and received either ASC hydrogel, ASC injection alone, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis. This experiment was repeated using CD26+/CD55+ FACS-enriched ASCs to further evaluate the regenerative potential of ASCs in wound healing. ASC hydrogel-treated burns demonstrated accelerated time to reepithelialization, greater vascularity, and increased expression of the proangiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the profibrotic gene Timp1 a...