Human Umbilical Cord–Derived Mesenchymal Stromal Cell Therapy Modulates Inflammation in Mine-Explosive Wounds in Humans: A Transcriptomic Study

Background The effective treatment of blast-related soft tissue injuries requires the development of innovative approaches. MSCs have demonstrated paracrine beneficial effects by regulating inflammation, modulating fibroblast activation and collagen production, and promoting neovascularization and re-epithelialization. This research focused on how wound functional status and transcriptome changed following umbilical cord-derived mesenchymal stromal cell transplantation in patients with mine explosive wounds of the lower limbs. Methods This study involved 7 patients following conventional wound treatment (control group) and 8 patients treated with a single dose of intra-wound injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) (MCS group). RNA-seq of wound biopsy specimens was used for transcriptome analysis, and selected mRNA expression levels were validated by real-time quantitative PCR (qPCR). Data was collected on the day of patient admission (day 0) and on the 1 ^st and 7 ^th days of follow-up. Surgical autoplasty was applied as a treatment method for wound closure. To assess potency, hUC-MSCs were co-cultured with various immune cells, followed by flow cytometry and qPCR analyses. Results In the present study, we demonstrated that hUC-MSCs transplantation was safe and did not affect the wound healing rate or the efficiency of surgical autoplasty in patients with mine-explosive wounds within one week. hUC-MSCs injections exerted anti-inflammatory effects in wounds at the transcriptomic level. Gene expression changes observed in macrophages and CD4⁺ T cells in MSC co-culture models further support the immunomodulatory potency of hUC-MSCs in attenuating inflammation in mine-explosive wounds. Conclusions hUC-MSCs transplantation was shown to be safe and did not adversely affect wound healing or surgical autoplasty outcomes, while demonstrating pronounced anti-inflammatory effects within one week of observation. Trial registration This study was conducted as a prospective, single-center, open-label, non-randomized clinical study. All procedures were performed in accordance with the Declaration of Helsinki and were approved by the local Ethics Committee of O.O. Shalimov National Scientific Center of Surgery and Transplantology (protocol #10/05/2024).