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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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 (ρ0) 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 ρ0 cells. Thus, ultrapure, homogenous, and safe stem cell RECs could provide a potential therapeutic tool for diseases associated with mitochondrial dysfunction.

Details

Title
Extracellular Vesicles and Cx43-Gap Junction Channels Are the Main Routes for Mitochondrial Transfer from Ultra-Purified Mesenchymal Stem Cells, RECs
Author
Yang, Jiahao 1   VIAFID ORCID Logo  ; Liu, Lu 1 ; Oda, Yasuaki 1 ; Wada, Keisuke 1 ; Ago, Mako 1 ; Matsuda, Shinichiro 2 ; Hattori, Miho 1 ; Goto, Tsukimi 1 ; Ishibashi, Shuichi 3 ; Kawashima-Sonoyama, Yuki 1 ; Matsuzaki, Yumi 4 ; Taketani, Takeshi 1 

 Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan; [email protected] (J.Y.); [email protected] (L.L.); [email protected] (Y.O.); [email protected] (K.W.); [email protected] (M.A.); [email protected] (M.H.); [email protected] (T.G.); [email protected] (Y.K.-S.) 
 Department of Medical Oncology, Shimane University Hospital, 89-1 Enya-cho, Izumo 693-8501, Japan; [email protected] 
 Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan; [email protected] 
 Department of Life Science, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan; [email protected] 
First page
10294
Publication year
2023
Publication date
2023
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2829821493
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.