Human-adipose Xenografts Improve Burn Wound Healing In Mice
Fuat Baris Bengur, MD1, Shawn J. Loder, MD1, Lauren Kokai, PhD1, J Peter Rubin, MD2.
1University of Pittsburgh, Pittsburgh, PA, USA, 2University of Pittsburgh, PITTSBURGH, PA, USA.
BACKGROUND: Acute treatment of complex burns remains a critically unmet need. Adipose and adipose-derived stem cell therapies have met success in the treatment of acute and sub-acute thermal injuries; however, the exact mechanism or effective agent is still under exploration. Prior reports vary highly as to whether a healthy autologous vascular fraction is necessary or whether xenologous, decellularized, or fractionated adipose extracts may be used - with implications for the possibility of off-the-shelf adipose-derived therapeutics for complex burns.
METHODS: Female athymic mice sustained bilateral 1 cm full-thickness thermal injury and were stratified into either ipsilateral untreated burn controls or contralateral xenograft-adipose treatment. 300 ul of human 1.0 mm lipoaspirate was injected subcutaneously immediately post-burn to treatment-stratified wounds. Mice were followed photographically for 4-to-6-weeks. At sacrifice wound biopsies were collected for H&E, Trichrome, and protein.
RESULTS: In mice treated with adipose xenograft at time of burn we noted no difference in surface area or burn morphology at 1-week post-injury. By 2-weeks post injury more rapid resolution of inflammation and wound surface area was noted which achieved significance by 4-6 weeks in grafted wounds. Adipose engraftment resulted is histologic evidence of scar resolution with consistent revascularization and survival of the subcutaneous adipose xenograft at 6-weeks.
CONCLUSIONS: In contrast to prior data suggesting an autologous-only approach, our findings support a hypothesis that the active functional agent in adipose xenograft for burns in not directly dependent on species match. This provides evidence to support more broadly applicable approach to adipose-derived therapeutics in acute burns.
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