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

Yeo Min Yoon, Jun Hee Lee, Keon Hyoung Song, Hyunjin Noh, Sang Hun Lee

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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.

Original languageEnglish
Article numbere12632
JournalJournal of Pineal Research
Volume68
Issue number3
DOIs
StatePublished - 1 Apr 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • cellular prion protein
  • chronic kidney diseases
  • exosome
  • ischemic disease
  • melatonin
  • mesenchymal stem/stromal cells

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