Dong Hu1,2,3, Deying Zhang4,5, Bo Liu1,2, Yang Liu6, Yu Zhou1,2, Yihang Yu1,2, Lianju Shen2, Chunlan Long2, Dan Zhang2, Xing Liu1,2, Tao Lin1,2, Dawei He1,2, Tao Xu7, Peter Timashev8, Denis Butnaru9, Yuanyuan Zhang10, Guanghui Wei11,12. 1. Department of Urology, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. 2. Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. 3. Department of Pediatric Surgery, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, 611731, Chengdu, China. 4. Department of Urology, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. zdy@hospital.cqmu.edu.cn. 5. Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. zdy@hospital.cqmu.edu.cn. 6. Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, 510655, Guangzhou, China. 7. Bio-manufacturing Center, Department of Mechanical Engineering, Tsinghua University, 100084, Beijing, China. 8. Institute for Regenerative Medicine, Sechenov University, 8-2 Trubetskaya Street, 119991, Moscow, Russia. 9. Research Institute for Uronephrology, Sechenov First Moscow State Medical University, 119991, Moscow, Russia. 10. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA. 11. Department of Urology, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. u806806@cqmu.deu.cn. 12. Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China. u806806@cqmu.deu.cn.
Abstract
BACKGROUND: Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. METHODS: Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-β (TGF-β)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. RESULTS: The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-β/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. CONCLUSIONS: The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-β/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.
BACKGROUND:Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. METHODS:Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-β (TGF-β)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. RESULTS: The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-β/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. CONCLUSIONS: The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-β/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.