Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis

  • Inflammation. 2024 Apr 25. doi: 10.1007/s10753-024-02027-0.
Qitong Guo  1  2 ,  Ping Li  1  2 ,  Meiling Chen  1  2 ,  Yihang Yu  1  2 ,  Yonghong Wan  1  2 ,  Zhaoxia Zhang  1  2 ,  Chunnian Ren  1  2 ,  Lianju Shen  1  2 ,  Xing Liu  1  2 ,  Dawei He  1  2 ,  Yuanyuan Zhang  3 ,  Guanghui Wei  1  2 ,  Deying Zhang  4  5
Affiliations
  • 1. Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
  • 2. National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China.
  • 3. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
  • 4. Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. [email protected].
  • 5. National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China. [email protected].
PMID: 38662165 DOI: 10.1007/s10753-024-02027-0
Abstract

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-β (TGF-β) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA Sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.

Keywords
chronic kidney disease; human umbilical cord mesenchymal stem cell-derived exosome; macrophage to myofibroblast transformation; renal fibrosis.
Products
Inhibitors & Agonists
Other Products