Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

AIM To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection. METHODS Lewis rat BMMSCs were cultured in vitro. Third-passage BMMSCs were transduced with the CXCR3 / HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to small bowel transplant. Six time points (instant, 1 d, 3 d, 7 d, 10 d, and 14 d) (n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines. RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group (53 d) was significantly longer than that of the HO-1 modified BMMSCs group (39 d), the BMMSCs group (26 d), and the NS group (control group) (16 d) (P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3 / HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased (P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-gamma, and TNF-alpha levels were significantly decreased and the levels of IL-10 and TGF-beta were significantly increased (P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.

Cu(II)-baicalein enhance paracrine effect and regenerative function of stem cells in patients with diabetes

The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy.In this study,the stemness and functionality of adipose stem cells derived from type 1 diabetic donors(T1DM-ASC)were enhanced by treatment with Cu(II)-baicalein microflowers(Cu-MON).After treatment with Cu-MON,T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion.Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC(CMTA),some genes were also expressed in HUVEC,Myoblast,Myofibroblast,and Vascular Smooth Muscle cells,inferring the common role of these cell types.In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors(ND-ASC)at a 15%cell dose,greatly reducing the treatment cost.Taken together,these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes,including paracrine effects.