Topical Gel Containing TNF-α-Activated Mesenchymal Stem Cell Secretome (MSC-CM-T) Increases HMGB1 Expression and Promotes Wound Healing in Full-Thickness Skin Defect Animal Model

Abstract

Mesenchymal stem cell conditioned medium or secretome contained several growth factors and cytokines that promote wound healing, thus topical gel containing TNF-α-activated MSC secretome (MSC-CM-T) may be considered as a promising candidate for the treatment of cutaneous wounds. This study aimed to investigate the benefit of MSC-CM-T in promoting wound healing by evaluating changes in wound closure percentage and HMGB1 gene expression. Eighteen Wistar rats were randomly assigned to treatment group receiving 200 µL MSC-CM-T topical gel (9 subjects) and control group receiving 200 µL serum-free DMEM topical gel (9 subjects). A 6 cm incision wounds were made on their backs, and treatment were given twice daily for 6 days. Wound closure were measured using standard calliper, and HMGB1 gene expression were evaluated using quantitative Real-Time PCR. The treatment group showed higher increase of wound closure percentages ( wound closure 46,11±4,41 vs 20.57±6.87 %; p<0.001), HMGB1 expression on day 3 (11.630.28 vs 10.830.31 fc; p<0.001) and day 6 (12.730.29 vs 11.870.31 fc; p<0.001), and  HMGB1 expression between day 0–3 (2.650.66 vs 1.810.69 fc; p<0.05) and day 0–6 (3.740.77 vs 2.850.72 fc; p<0.05). This study also found a strong positive correlation between wound closure percentages and HMGB1 expression on both day 3 (r = 0.7231; p<0.001) and day 6 (r = 0.7262; p<0.001). Based on these results, it can be concluded that MSC-CM-T may potentially promote faster wound healing, with HMGB1 as one of the possible factor that mediates this effect.