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Journal Article Epublish 4 citations

PubMed: 39080774 DOI: 10.1186/s13287-024-03845-7

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

Stem Cell Res Ther 15(1):240

Authors: Reyhaneh Toghiani, Vajihe Azimian Zavareh, Hanyieh Najafi, Mina Mirian, Negar Azarpira, Samira Sadat Abolmaali, Jaleh Varshosaz, Ali Mohammad Tamaddon

Affiliations

  • Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Department of Plant and Animal Biology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran.
  • Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

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.

MeSH

Cells, Microscopy, Electron, Scanning Transmission, Stem Cells, Exosomes, Reperfusion, Hypoxia, Reperfusion Injury, Therapeutics, Ischemia

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