Bone marrow–derived mesenchymal stem cells attenuate tubulointerstitial injury through multiple mechanisms in UUO model

• Published in: Journal of cellular biochemistry Vol. 120; no. 6; pp. 9737 - 9746
• Main Authors: Xing, Li, Song, Erlin, Yu, Cheng Yuan, Jia, Xi Bei, Ma, Jing, Sui, Man Shu, Wang, Ming Ao, Gao, Xu
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2019
• Subjects: Attenuation; Bone marrow; bone marrow–derived mesenchymal stem cells (MSCs); Cell activation; Cell growth; Cell proliferation; Fibrosis; Histology; Infiltration; Kidney diseases; Kidneys; Macrophages; Mesenchymal stem cells; Mesenchyme; renal fibrosis; renoprotective effect; Stem cell transplantation; Stem cells; Surgery; Therapeutic applications; tubulointerstitial; unilateral ureteral obstruction (UUO); unilateral ureteral obstruction (UUO); tubulointerstitial; renal fibrosis; bone marrow-derived mesenchymal stem cells (MSCs); renoprotective effect
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28254

Current evidence supports the use of bone marrow–derived mesenchymal stem cells (MSCs) for a diverse range of clinical applications, and many studies have shown that MSCs have renal‐protective effects, but the mechanism is not well understood. Therefore, in this study, we aim to further identify whether MSCs can attenuate renal fibrosis by decreasing tubulointerstitial injury in a unilateral ureteral obstruction (UUO) model. In this study, we cultured MSCs and then transplanted them into a UUO model through the tail vein. Histology, cell proliferation, peritubular capillary (PTC) loss and myofibroblast markers were examined on days 3, 7 and 14 after surgery. We demonstrated that renal interstitial fibrosis in the MSC group was significantly attenuated compared with the UUO and DMEM groups. Moreover, MSC treatment inhibited the loss of PTCs and increased parenchymal cell proliferation. In addition, UUO‐induced activation and proliferation of myofibroblasts were suppressed by MSC infusion. Furthermore, MSCs attenuated tubulointerstitial infiltration of macrophages in UUO mice. Tubulointerstitial damage plays a very important role in the progression of chronic kidney disease (CKD). PTC loss, macrophage recruitment, and myofibroblast activation are directly correlated with the development of renal tubulointerstitial fibrosis. Our results suggest that MSC infusion in the UUO model is a promising therapeutic strategy for promoting kidney repair. Our research indicate that the MSC infusion is a promising therapeutic strategy for CKD.