PMID- 31989677
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 68
IP  - 3
DP  - 2020 Apr
TI  - Melatonin-stimulated exosomes enhance the regenerative potential of chronic 
      kidney disease-derived mesenchymal stem/stromal cells via cellular prion 
      proteins.
PG  - e12632
LID - 10.1111/jpi.12632 [doi]
AB  - 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 
      (PrP(C) ) 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-PrP(C) 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 PrP(C) could be key molecules for enhancing the 
      regenerative potential of MSCs in ischemic diseases.
CI  - (c) 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Yoon, Yeo Min
AU  - Yoon YM
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul, Korea.
FAU - Lee, Jun Hee
AU  - Lee JH
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul, Korea.
AD  - Departments of Biochemistry, Soonchunhyang University College of Medicine, 
      Cheonan, Korea.
FAU - Song, Keon-Hyoung
AU  - Song KH
AD  - Department of Pharmaceutical Engineering, College of Medical Science, 
      Soonchunhyang University, Asan, Korea.
FAU - Noh, Hyunjin
AU  - Noh H
AD  - Department of Internal Medicine, Soonchunhyang University, Seoul, Korea.
AD  - Hyonam Kidney Laboratory, Soonchunhyang University, Seoul, Korea.
FAU - Lee, Sang Hun
AU  - Lee SH
AUID- ORCID: 0000-0002-6626-9702
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul, Korea.
AD  - Departments of Biochemistry, Soonchunhyang University College of Medicine, 
      Cheonan, Korea.
LA  - eng
GR  - NRF-2017M3A9B4032528/National Research Foundation of Korea/
GR  - NRF-2019M3A9H1103495/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20200217
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (MIRN-4516 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Prion Proteins)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Exosomes/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Melatonin/*pharmacology
MH  - Mesenchymal Stem Cell Transplantation/methods
MH  - Mesenchymal Stem Cells/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*metabolism
MH  - Prion Proteins/*metabolism
MH  - *Renal Insufficiency, Chronic
OTO - NOTNLM
OT  - cellular prion protein
OT  - chronic kidney diseases
OT  - exosome
OT  - ischemic disease
OT  - melatonin
OT  - mesenchymal stem/stromal cells
EDAT- 2020/01/29 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/01/29 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2020/01/07 00:00 [revised]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/01/29 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/01/29 06:00 [entrez]
AID - 10.1111/jpi.12632 [doi]
PST - ppublish
SO  - J Pineal Res. 2020 Apr;68(3):e12632. doi: 10.1111/jpi.12632. Epub 2020 Feb 17.