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Related Concept Videos

Mesenchymal Stem Cells01:19

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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
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Mesenchymal Stem/Stromal Cells and their Extracellular Vesicle Progeny Decrease Injury in Poststenotic Swine Kidney

Yu Zhao1,2, Xiangyang Zhu2, Lei Zhang2,3

  • 1Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China.

Stem Cells and Development
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Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) both improve kidney function and reduce injury in a pig model of chronic kidney disease. MSCs better preserved microvasculature, while EVs enhanced cellular integrity.

Keywords:
extracellular vesiclesmesenchymal stem cellsrenal artery stenosis

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Area of Science:

  • Nephrology
  • Regenerative Medicine
  • Cell Biology

Background:

  • Chronic kidney disease (CKD) prevalence is rising, necessitating novel therapeutic strategies.
  • Mesenchymal stem/stromal cells (MSCs) and their derived extracellular vesicles (EVs) show promise in tissue repair.
  • The comparative efficacy and distinct mechanisms of MSCs versus EVs in renal protection remain to be fully elucidated.

Purpose of the Study:

  • To test the hypothesis that EVs are as effective as MSCs in protecting the stenotic kidney but target different injury pathways.
  • To evaluate the therapeutic potential of adipose tissue-derived MSCs and their EVs in a preclinical pig model of metabolic syndrome and renal artery stenosis (MetS + RAS).

Main Methods:

  • A pig model of MetS + RAS was established, with subsequent intrarenal delivery of autologous MSCs or EVs.
  • Renal function was assessed in vivo using CT and MRI, alongside ex vivo histopathology and molecular marker analysis (necroptosis, inflammation, growth factors).
  • Lean pigs and sham RAS served as control groups.

Main Results:

  • Both MSCs and EVs improved stenotic kidney function, decreasing hypoxia, fibrosis, and apoptosis.
  • MSCs showed a slight advantage in preserving microvascular density and reducing inflammation.
  • EVs demonstrated a more significant upregulation of growth factors and a greater reduction in necroptosis.

Conclusions:

  • Adipose tissue-derived MSCs and their EVs both ameliorate renal injury and improve function in MetS + RAS pigs through partially distinct mechanisms.
  • MSCs excel at preserving microcirculation, whereas EVs offer superior protection of renal cellular integrity.
  • These findings support further investigation into MSCs and EVs as a novel therapeutic approach for attenuating renal injury.