Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles as Natural Nanocarriers in the Treatment of Nephrotoxic Injury In Vitro

Cells. 2024 Oct 7;13(19):1658. doi: 10.3390/cells13191658.

Abstract

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases.

Objective: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro.

Method: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated.

Results: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage.

Conclusions: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.

Keywords: miRNA-126 and anti-miRNA-126; natural nanocarriers; umbilical cord mesenchymal stem cell-derived extracellular vesicles.

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • DNA Damage
  • Extracellular Vesicles* / metabolism
  • Extracellular Vesicles* / transplantation
  • Humans
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Rats
  • Umbilical Cord* / cytology

Substances

  • MicroRNAs