The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage M1/M2 polarization.

A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.

Can radiomics replace the SPARCC scoring system in evaluating bone marrow edema of sacroiliac joints in patients with axial spondyloarthritis?

OBJECTIVES: To develop an objective and efficient method based on radiomics to evaluate bone marrow edema (BMO) of sacroiliac joints (SIJs) by magnetic resonance imaging (MRI) in patients with axial spondyloarthritis (axSpA) and to compare with the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. METHODS: From September 2013 to March 2022, patients with axSpA who underwent 3.0T SIJ-MRI were included and were randomly divided into training and validation cohorts at a ratio of 7:3. The optimal radiomics features selected from the SIJ-MRI in the training cohort were included to generate the radiomics model. The performance of the model was evaluated by ROC analysis and decision curve analysis (DCA). Rad scores were calculated using the radiomics model. The responsiveness was compared for Rad scores and SPARCC scores. We also assessed the correlation between the Rad score and SPARCC score. RESULTS: A total of 558 patients were finally included. The radiomics model showed favorable discrimination of a SPARCC score <2 or ≥2 both in the training (AUC, 0.90; 95% CI: 0.87-0.93) and validation cohorts (AUC, 0.90; 95% CI, 0.86-0.95). DCA confirmed that the model was clinically useful. Rad score showed higher responsiveness to treatment-related change than SPARCC score. Furthermore, a significant correlation was noted between the Rad score and SPARCC score when scoring the status of BMO (rs=0.80, P < 0.001), and a strong correlation was noted when scoring the change in BMO (r=0.70, P < 0.001). CONCLUSION: The study proposed a radiomics model to accurately quantify the BMO of SIJs in patients with axSpA, providing an alternative to the SPARCC scoring system. Key Points • The Rad score is an index with high validity for the objective and quantitative evaluation of bone marrow edema (BMO) of the sacroiliac joints in axial spondyloarthritis. • The Rad score is a promising tool to monitor the change of BMO upon treatment.