PMID- 37373439
OWN - NLM
STAT- MEDLINE
DCOM- 20230629
LR  - 20230701
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 12
DP  - 2023 Jun 18
TI  - Extracellular Vesicles and Cx43-Gap Junction Channels Are the Main Routes for 
      Mitochondrial Transfer from Ultra-Purified Mesenchymal Stem Cells, RECs.
LID - 10.3390/ijms241210294 [doi]
LID - 10294
AB  - Mitochondria are essential organelles for maintaining intracellular homeostasis. 
      Their dysfunction can directly or indirectly affect cell functioning and is 
      linked to multiple diseases. Donation of exogenous mitochondria is potentially a 
      viable therapeutic strategy. For this, selecting appropriate donors of exogenous 
      mitochondria is critical. We previously demonstrated that ultra-purified bone 
      marrow-derived mesenchymal stem cells (RECs) have better stem cell properties and 
      homogeneity than conventionally cultured bone marrow-derived mesenchymal stem 
      cells. Here, we explored the effect of contact and noncontact systems on three 
      possible mitochondrial transfer mechanisms involving tunneling nanotubes, 
      connexin 43 (Cx43)-mediated gap junction channels (GJCs), and extracellular 
      vesicles (Evs). We show that Evs and Cx43-GJCs provide the main mechanism for 
      mitochondrial transfer from RECs. Through these two critical mitochondrial 
      transfer pathways, RECs could transfer a greater number of mitochondria into 
      mitochondria-deficient (rho(0)) cells and could significantly restore mitochondrial 
      functional parameters. Furthermore, we analyzed the effect of exosomes (EXO) on 
      the rate of mitochondrial transfer from RECs and recovery of mitochondrial 
      function. REC-derived EXO appeared to promote mitochondrial transfer and slightly 
      improve the recovery of mtDNA content and oxidative phosphorylation in rho(0) 
      cells. Thus, ultrapure, homogenous, and safe stem cell RECs could provide a 
      potential therapeutic tool for diseases associated with mitochondrial 
      dysfunction.
FAU - Yang, Jiahao
AU  - Yang J
AUID- ORCID: 0000-0001-5878-4563
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Liu, Lu
AU  - Liu L
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Oda, Yasuaki
AU  - Oda Y
AUID- ORCID: 0009-0003-4452-9248
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Wada, Keisuke
AU  - Wada K
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Ago, Mako
AU  - Ago M
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Matsuda, Shinichiro
AU  - Matsuda S
AD  - Department of Medical Oncology, Shimane University Hospital, 89-1 Enya-cho, Izumo 
      693-8501, Japan.
FAU - Hattori, Miho
AU  - Hattori M
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Goto, Tsukimi
AU  - Goto T
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Ishibashi, Shuichi
AU  - Ishibashi S
AD  - Department of Digestive and General Surgery, Faculty of Medicine, Shimane 
      University, 89-1 Enya-cho, Izumo 693-8501, Japan.
FAU - Kawashima-Sonoyama, Yuki
AU  - Kawashima-Sonoyama Y
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
FAU - Matsuzaki, Yumi
AU  - Matsuzaki Y
AD  - Department of Life Science, Faculty of Medicine, Shimane University, 89-1 
      Enya-cho, Izumo 693-8501, Japan.
FAU - Taketani, Takeshi
AU  - Taketani T
AD  - Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, 
      Izumo 693-8501, Japan.
LA  - eng
GR  - 18K15673/JSPS, Grants-in-Aid for Scientific Research (KAKENHI)/
GR  - JPMJSP2155/JST SPRING/
PT  - Journal Article
DEP - 20230618
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Tunneling Nanotubes)
RN  - 0 (Connexin 43)
RN  - 0 (Ion Channels)
SB  - IM
MH  - Connexin 43/genetics/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - Mitochondria/metabolism
MH  - Ion Channels/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Gap Junctions/metabolism
PMC - PMC10299354
OTO - NOTNLM
OT  - Cx43-gap junction channels (Cx43-GJCs)
OT  - extracellular vesicles (Evs)
OT  - mesenchymal stem cells (MSCs)
OT  - mitochondrial transfer
OT  - rapidly expanding clones (RECs)
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/29 06:42
PMCR- 2023/06/18
CRDT- 2023/06/28 01:20
PHST- 2023/04/21 00:00 [received]
PHST- 2023/06/10 00:00 [revised]
PHST- 2023/06/16 00:00 [accepted]
PHST- 2023/06/29 06:42 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:20 [entrez]
PHST- 2023/06/18 00:00 [pmc-release]
AID - ijms241210294 [pii]
AID - ijms-24-10294 [pii]
AID - 10.3390/ijms241210294 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jun 18;24(12):10294. doi: 10.3390/ijms241210294.