Human ucMSCs seeded in a decellularized kidney scaffold attenuate renal fibrosis by reducing epithelial–mesenchymal transition via the TGF-β/Smad signaling pathway,Pediatric Research

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Human ucMSCs seeded in a decellularized kidney scaffold attenuate renal fibrosis by reducing epithelial–mesenchymal transition via the TGF-β/Smad signaling pathway
Pediatric Research ( IF 3.1 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41390-019-0736-6
Dong Hu _{1,

2,

3} , Deying Zhang _{1,

2} , Bo Liu _{1,

2} , Yang Liu ₄ , Yu Zhou _{1,

2} , Yihang Yu _{1,

2} , Lianju Shen ₂ , Chunlan Long ₂ , Dan Zhang ₂ , Xing Liu _{1,

2} , Tao Lin _{1,

2} , Dawei He _{1,

2} , Tao Xu ₅ , Peter Timashev ₆ , Denis Butnaru ₇ , Yuanyuan Zhang ₈ , Guanghui Wei _{1,

2}

Affiliation

Department of Urology, Children's Hospital of Chongqing Medical University, 400014, Chongqing, China.
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.
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.
Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, 510655, Guangzhou, China.
Bio-manufacturing Center, Department of Mechanical Engineering, Tsinghua University, 100084, Beijing, China.
Institute for Regenerative Medicine, Sechenov University, 8-2 Trubetskaya Street, 119991, Moscow, Russia.
Research Institute for Uronephrology, Sechenov First Moscow State Medical University, 119991, Moscow, Russia.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.

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.

中文翻译：

接种在脱细胞肾支架中的人 ucMSCs 通过 TGF-β/Smad 信号通路减少上皮 - 间充质转化来减轻肾纤维化

背景肾纤维化主要通过上皮间质转化 (EMT) 发生。本研究探讨了载有人脐带间充质干细胞的脱细胞肾支架 (ucMSC-DKS) 对移植后肾功能衰竭啮齿动物模型中肾纤维化的有益作用及其潜在机制。方法制备后检查大鼠来源的DKSs，然后用人ucMSCs再细胞化制备细胞负载贴片。肾次全切除术（STN）后建立大鼠肾功能衰竭模型。细胞贴片被移植到残肾。与非细胞补片对照相比，在手术后 8 周检查肾功能、组织学、EMT 和残肾中与转化生长因子-β（TGF-β）/Smad 信号通路相关的蛋白质的变化。结果DKSs是无细胞和多孔的，具有丰富的细胞因子和主要的细胞外基质成分。ucMSCs 均匀分布在 DKSs 中。ucMSC-DKS补片移植后8周与对照组相比，肾功能改善，肾纤维化和EMT减少，TGF-β/Smad信号通路受到抑制。结论 ucMSC-DKS 可通过 TGF-β/Smad 信号通路减少已接受 STN 的大鼠的 EMT，从而恢复肾功能并减少纤维化。它为肾纤维化治疗提供了一种替代方案。ucMSC-DKS贴片移植后8周与对照组相比，TGF-β/Smad信号通路被抑制。结论 ucMSC-DKS 可通过 TGF-β/Smad 信号通路减少已接受 STN 的大鼠的 EMT，从而恢复肾功能并减少纤维化。它为肾纤维化治疗提供了一种替代方案。ucMSC-DKS贴片移植后8周与对照组相比，TGF-β/Smad信号通路被抑制。结论 ucMSC-DKS 可通过 TGF-β/Smad 信号通路减少已接受 STN 的大鼠的 EMT，从而恢复肾功能并减少纤维化。它为肾纤维化治疗提供了一种替代方案。

更新日期：2020-01-02

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