Secretome of Human MSC Gel Improves DFU Healing through NF-?B p50 and CD163 mRNA Expression

<b>Background and Objective:</b> Diabetic foot ulcers (DFUs) remain a critical clinical problem and stem cell-derived secretome reared under hypoxic conditions has been shown to play a significant role in tissue repair via immunomodulation. This study aimed to evaluate the secretome of human mesenchymal stem cell gel (SH-MSC gel) in DFU patients with grades 2 and 3 through reduced wound volume and modulation of CD163 and NF-κB p50 mRNA expression. <b>Materials and Methods:</b> A prospective, randomized controlled clinical trial involved 16 DFU patients with grades 2 and 3. Participants received either a placebo gel or an intervention gel containing secretome from Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) cultured under hypoxic conditions. All patients received standard wound care. Primary outcomes included changes in wound volume and expression levels of CD163 and NF-κB p50 mRNA in wound tissue, assessed using quantitative PCR. The Shapiro-Wilk test assessed normality and for normally distributed data, paired t-tests (within-group) and unpaired t-tests (between-group) were used. One-way ANOVA compared means across groups, while the Kruskal-Wallis test followed by <i>post hoc</i> analysis was employed for non-parametric data (p<0.05). Statistical analysis was performed using GraphPad Prism 10. <b>Results:</b> Baseline characteristics of participants did not show significant differences between the groups. Treatment with SH-MSC gel significantly enhanced wound healing compared to the placebo group, evidenced by a marked reduction in wound volume after 7 days (95% CI (0.467 to 1.18), p<0.001). The CD163 mRNA expression significantly increased in the SH-MSC gel group post-treatment (95% CI (-2.20 to -1.11), p<0.001), while NF-κB p50 mRNA expression significantly decreased (95% CI (0.349 to 0.688), p<0.001). <b>Conclusion:</b> The clinical trial results suggested that SH-MSC gel effectively improves wound healing in DFUs. Further research is warranted to explore additional inflammatory markers to better understand DFU treatment.