26dkou344 10.3205/26dkou344 urn:nbn:de:0183-26dkou3443 Meeting Abstract Xu Xu Chengfeng C

The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China

author German Medical Science GMS Publishing House

Düsseldorf

610 20261020 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0659 344 Deutsche Gesellschaft für Orthopädie und Unfallchirurgie Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie Deutsche Gesellschaft für Unfallchirurgie Berufsverband für Orthopädie und Unfallchirurgie Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2026) Grundlagenforschung | Geweberegeneration Berlin 20261020 20261023 DKOU26_Abs_2232 TextObjectives and questions: Allogeneic skin coverage is often required after extensive burns/trauma when donor sites are limited, but immune rejection shortens graft survival. BMSCs are immunomodulatory yet may be insufficient at standard dosing. COX-2 enhances PGE2 production and supports Treg-mediated tolerance. We investigated whether COX-2 gene engineering enhances BMSC immunomodulation to suppress allo-reactive T-cell responses, shift the Treg/Th17 balance toward tolerance, and prolong skin allograft survival after scald injury.Material and methods: Murine BMSCs (Balb/c) were isolated and genetically modified for COX-2 overexpression or siRNA knockdown; COX-2 expression was verified by qPCR/Western blot and PGE2 secretion by multiplex assays. Allo-reactive CD4+CD62L+ T-cell proliferation was assessed by flow cytometry in a dose-response co-culture system (BMSC:effector ratios 1:20, 1:10, 1:5; n=5/group). Mixed lymphocyte reaction (MLR) quantified Tregs and cytokines (PGE2, IL-10, IL-6, IL-17A). In vivo, C57BL/6J recipients received IV BMSCs for 4 consecutive days (total 1×10^6 cells/mouse), followed by a standardized 90°C scald injury (7 s) and skin grafting (1×1 cm). Groups: autograft, allograft control (Balb/c), allograft + unmodified BMSCs, allograft + COX-2–BMSCs, and COX-2–BMSCs + third-party allograft (C3H) (n=20/group). Graft survival was analyzed by log-rank testing; day-8 samples underwent histology, flow cytometry, and multiplex cytokines (p<0.05).Results: COX-2 overexpression increased PGE2 secretion, whereas knockdown reduced it. In allo-reactive proliferation assays, stimulated T-cell proliferation was 54.20±2.23%. Unmodified BMSCs reduced proliferation to 42.21±1.23%, 33.53±3.26%, and 25.23±2.68% (1:20–1:5), while COX-2–BMSCs further suppressed proliferation to 36.15±1.56%, 25.66±2.32%, and 15.13±2.75% at matched ratios (all p<0.05 vs unmodified). In MLR, Tregs increased from 1.22±0.25% (control) to 5.77±1.45% (BMSCs) and 8.76±1.56% (COX-2–BMSCs) (p<0.05), accompanied by increased IL-10 and reduced IL-6/IL-17A. In the scald-plus-grafting model, mean graft survival was 10.6±0.55 days (allograft control), 13.4±1.14 days (BMSCs), and 14.6±1.82 days (COX-2–BMSCs), while autografts survived throughout the 30-day observation. COX-2–BMSCs increased Tregs (20.8±2.5% vs 15.5±3.5% with unmodified BMSCs) and shifted systemic cytokines toward tolerance (IL-10: 23.06±3.32 vs 14.22±2.35; IL-6: 37.07±8.95 vs 87.36±5.78; IL-17A: 19.23±2.56 vs 44.57±1.05; all p<0.05).Discussion and conclusions: COX-2 gene engineering enhances BMSC-mediated immunomodulation, suppressing allo-reactive T-cell proliferation and promoting a tolerance-favoring Treg/Th17 shift, consistent with a PGE2/IL-10–linked mechanism. In a clinically relevant scald-plus-grafting model, COX-2–BMSCs significantly prolonged skin allograft survival and reduced rejection-associated inflammation. This cell-and-gene therapy strategy may extend temporary allograft coverage time after severe burns/trauma and serve as a bridge to definitive autologous reconstruction. 0 0 0 0