Adipose-derived stem cells improve grafted burn wound healing by promoting wound bed blood flow

Author:

Fujiwara Osamu1,Prasai Anesh23,Perez-Bello Dannelys1,El Ayadi Amina234,Petrov Irene Y5,Esenaliev Rinat O156,Petrov Yuriy5,Herndon David N23,Finnerty Celeste C234,Prough Donald S1,Enkhbaatar Perenlei13

Affiliation:

1. Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA

2. Department of Surgery, University of Texas Medical Branch, Galveston, 301 University BLVD TX 77555, USA

3. Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA

4. Sealy Center for Molecular Medicine, and the Institute for Translational Sciences, University of Texas Medical Branch, 301 University BLVD Galveston, TX 77555, USA

5. Center for Biomedical Engineering, University of Texas Medical Branch, 601 Harbor Side Dr. Galveston, TX 77555, USA

6. Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, 301 University BLVD Galveston, TX 77555, USA

Abstract

Abstract Background Researchers have explored the use of adipose-derived stem cells (ASCs) as a cell-based therapy to cover wounds in burn patients; however, underlying mechanistic aspects are not completely understood. We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways. Methods To test the hypothesis, we used an ovine burn model. A 5 cm2 full thickness burn wound was induced on each side of the dorsum. After 24 hours, the burned skin was excised and a 2 cm2 patch of autologous donor skin was grafted. The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment (phosphate-buffered saline [PBS]). Effects of ASCs culture media was also compared to those of PBS. Wound healing was assessed at one and two weeks following the application of ASCs. Allogeneic ASCs were isolated, cultured and characterized from non-injured healthy sheep. The identity of the ASCs was confirmed by flow cytometry analysis, differentiation into multiple lineages and gene expression via real-time polymerase chain reaction. Wound blood flow, epithelialization, graft size and take and the expression of vascular endothelial growth factor (VEGF) were determined via enzyme-linked immunosorbent assay and Western blot. Results Treatment with ASCs accelerated the patch graft growth compared to the control (p < 0.05). Topical application of ASCs significantly increased wound blood flow (p < 0.05). Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control (p < 0.05). Conclusions ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.

Funder

Shriners Hospitals for Children

National Institutes of Health

Clinical and Translational Science

Publisher

Oxford University Press (OUP)

Subject

Critical Care and Intensive Care Medicine,Dermatology,Biomedical Engineering,Emergency Medicine,Immunology and Allergy,Surgery

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