Effect ofCXCR3/HO-1genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

Abstract

AIMTo 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.METHODSLewis 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.RESULTSThe 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-γ, and TNF-α levels were significantly decreased and the levels of IL-10 and TGF-β were significantly increased (P < 0.05).CONCLUSIONBMMSCs 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.

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

“…However, we did not perform any pathway blocking experiments and only demonstrated the role of monocytes. Our team previously studied the role of stem cells in the functioning of the corresponding immune cells of the innate and adaptive immunity in transplant recipients [30,45]. In future, we aim to study the role of other immune cells by blocking major signaling pathways.…”

“…Isolation and identification of BMMSCs was performed as previously described [30,31]. BMMSCs transfected with Ad/HO-1 showed no morphological changes, with a typical spindle-shaped appearance (Fig.…”

Protective effects of CXCR3/HO‑1 gene‑modified BMMSCs on damaged intestinal epithelial cells: Role of the p38‑MAPK signaling pathway

“…CXCR3 receptors bind to their specific ligands [monokine induced by interferon (IFN)-γ, IFN-γ-inducible protein 10 and IFN-γ-inducible T-cell α chemoattractant], and recruit CXCR3-expressing cells to the site of injury (16,17). It has been shown that, following transfection with the CXCR3 gene, BMMSCs are chemotactically directed to migrate to a transplanted intestine; this was shown by the increased homing of BMMSCs and inhibited chemotaxis of T cells to transplanted intestine, resulting in protective effects on the transplanted small bowel (18). In our preliminary study, HO-1 and CXCR3 genes were transfected into BMMSCs in vitro , and subsequently transfused into a rat model of rejection to small bowel transplantation.…”

“…In our preliminary study, HO-1 and CXCR3 genes were transfected into BMMSCs in vitro , and subsequently transfused into a rat model of rejection to small bowel transplantation. The results showed that the HO-1 and CXCR3 gene-modified BMMSCs were significantly increased in the damaged sites, and the function of the damaged intestine quickly recovered (18). However, the mechanism by which the recovery of intestinal function was achieved remains to be elucidated and requires further investigation.…”

“…However, whether the p38-MAPK signaling pathway is involved in the recovery of transplanted intestinal function by BMMSCs has not been reported. In addition, tumor necrosis factor (TNF)-α has been shown to be involved in the recovery of transplanted intestinal function by CXCR3/HO-1 gene-modified BMMSCs in rats (18). The rat intestinal epithelial crypt cell line-6 (IEC-6) cell line is derived from the intestinal crypt of normal rats, which can be applied to the in vitro investigation of intestinal mucosal injury (24).…”