Ruifang Han,Haiyi Zhou,Xingshan Liang,Siyi He,Xiaoming Sun,Yongge Guan,Yang Song
Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.
Li Wu,Dan Han,Jie Jiang,Xiaojie Xie,Xunran Zhao,Tengfei Ke,Wen Zhao,Liu Liu,Wei Zhao
After the facial nerve axotomy (FNA), the distal end of the axon would gradually decay and disappear. Accumulated evidence shows that transplantation of bone marrow mesenchymal stem cells (BMSCs) reveals potential in the treatment of nervous system diseases or injuries. This study is aimed at investigating the therapeutic effects of co-transplantation of BMSCs and monocytes in FNA. We found that co-culture significantly elevated the CD4+/CD8+ ratio and CD4+ CD25+ T cell proportion compared with monocytes transplantation, and enhanced the differentiation of BMSCs into neurons. After the cell transplantation, the lowest apoptosis in the facial nerve nucleus was found in the co-transplantation group 2 (BMSCs:monocytes= 1:30). Moreover, the lowest expression levels of pro-inflammatory cytokines and the highest expression levels of anti-inflammatory cytokines were observed in the co-transplantation group 2 (BMSCs: monocytes= 1:30). The highest expression levels of protein in the JAK/STAT6 pathway and the SDF-1/CXCR4 axis were found in the co-transplantation group 2. BMSC/monocyte co-transplantation significantly improves the microenvironment in the facial nerve nucleus in FNA rats; therefore these findings suggest that it could promote the anti-/pro-inflammatory balance shift towards the anti-inflammatory microenvironment, alleviating survival conditions for BMSCs, regulating BMSC the chemotaxis homing, differentiation, and the section of BMSCs, and finally reducing the neuronal apoptosis. These findings might provide essential evidence for the in-hospital treatment of FNA with co-transplantation of BMSCs and monocytes.
Cell-based therapeutic approaches have been proven to be effective strategies for the treatment of acute liver injury (ALI). However, widespread application of these procedures is limited by several key issues, including rapid loss of stemness in vitro, aberrant differentiation into undesirable cell types, and low engraftment in vivo. In this study, liver epithelial progenitor cells (LEPCs) were characterized and transfected with augmenter of liver regeneration (ALR). The results revealed that in ALI mice with CCl4, the transplantation of ALR-bearing LEPCs into the liver markedly protected mice against ALI by decreasing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thus relieving hepatic tissue injury and attenuating inflammatory infiltration. Mechanistically, the knockdown of ALR in LEPCs activated the phosphorylation of dynamin-related protein 1 (Drp1) at the S616 site and thereby enhanced mitochondrial fission. In contrast, the transfection of ALR into LEPCs significantly inhibited Drp1 phosphorylation, thereby favoring the maintenance of mitochondrial integrity and the preservation of adenosine triphosphate contents in LEPCs. Consequently, the ALR-bearing LEPCs transplanted into ALI mice exhibited substantially greater homing ability to the injured liver via the SDF-1/CXCR4 axis than that of LEPCs-lacking ALR. In conclusion, we demonstrated that the transplantation of ALR-transfected LEPCs protected mice against CCl4-induced ALI, thus offering immense curative potential in the clinic.
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