RRC ID 78860
著者 Yang J, Liu L, Oda Y, Wada K, Ago M, Matsuda S, Hattori M, Goto T, Ishibashi S, Kawashima-Sonoyama Y, Matsuzaki Y, Taketani T.
タイトル Extracellular Vesicles and Cx43-Gap Junction Channels Are the Main Routes for Mitochondrial Transfer from Ultra-Purified Mesenchymal Stem Cells, RECs.
ジャーナル Int J Mol Sci
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.
巻・号 24(12)
公開日 2023-6-18
DOI 10.3390/ijms241210294
PII ijms241210294
PMID 37373439
PMC PMC10299354
MeSH Connexin 43 / genetics Connexin 43 / metabolism Extracellular Vesicles* / metabolism Gap Junctions / metabolism Ion Channels / metabolism Mesenchymal Stem Cells* / metabolism Mitochondria / metabolism
リソース情報
ヒト・動物細胞 A549(RCB0098)