Hypoxia-preconditioned WJ-MSC spheroid-derived exosomes delivering miR-210 for renal cell restoration in hypoxia-reoxygenation injury

Stem Cell Res Ther. 2024 Jul 30;15(1):240. doi: 10.1186/s13287-024-03845-7.

Abstract

Background: Recent advancements in mesenchymal stem cell (MSC) technology have paved the way for innovative treatment options for various diseases. These stem cells play a crucial role in tissue regeneration and repair, releasing local anti-inflammatory and healing signals. However, challenges such as homing issues and tumorigenicity have led to exploring MSC-exosomes as a promising alternative. MSC-exosomes have shown therapeutic potential in conditions like renal ischemia-reperfusion injury, but low production yields hinder their clinical use.

Methods: To address this limitation, we examined hypoxic preconditioning of Wharton jelly-derived MSCs (WJ-MSCs) 3D-cultured in spheroids on isolated exosome yields and miR-21 expression. We then evaluated their capacity to load miR-210 into HEK-293 cells and mitigate ROS production, consequently enhancing their survival and migration under hypoxia-reoxygenation conditions.

Results: MiR-210 overexpression was significantly induced by optimized culture and preconditioning conditions, which also improved the production yield of exosomes from grown MSCs. The exosomes enriched with miR-210 demonstrated a protective effect by improving survival, reducing apoptosis and ROS accumulation in damaged renal cells, and ultimately promoting cell migration.

Conclusion: The present study underscores the possibility of employing advanced techniques to maximize the therapeutic attributes of exosomes produced from WJ-MSC spheroid for improved recovery outcomes in ischemia-reperfusion injuries.

Keywords: 3D culture; Exosome; Hypoxia preconditioning; Renal ischemia-reperfusion injury; Wharton jelly-derived mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Hypoxia
  • Cell Movement
  • Exosomes* / metabolism
  • HEK293 Cells
  • Humans
  • Kidney / metabolism
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / therapy
  • Spheroids, Cellular / metabolism
  • Wharton Jelly / cytology

Substances

  • MicroRNAs
  • MIRN210 microRNA, human
  • Reactive Oxygen Species