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Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins.

Abstract
Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome-treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrPC ) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome-treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome-treated CKD-MSCs via the miR-4516-PrPC signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrPC could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.
AuthorsYeo Min Yoon, Jun Hee Lee, Keon-Hyoung Song, Hyunjin Noh, Sang Hun Lee
JournalJournal of pineal research (J Pineal Res) Vol. 68 Issue 3 Pg. e12632 (Apr 2020) ISSN: 1600-079X [Electronic] England
PMID31989677 (Publication Type: Journal Article)
Copyright© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Chemical References
  • MIRN-4516 microRNA, human
  • MicroRNAs
  • Prion Proteins
  • Melatonin
Topics
  • Animals
  • Exosomes (drug effects, metabolism)
  • Female
  • Humans
  • Male
  • Melatonin (pharmacology)
  • Mesenchymal Stem Cell Transplantation (methods)
  • Mesenchymal Stem Cells (drug effects, metabolism)
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs (metabolism)
  • Prion Proteins (metabolism)
  • Renal Insufficiency, Chronic

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