{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:42:00Z","timestamp":1791772920659,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS Grants-in-Aid for Scientific Research (KAKENHI)","award":["23H02876"],"award-info":[{"award-number":["23H02876"]}]},{"name":"JSPS Grants-in-Aid for Scientific Research (KAKENHI)","award":["JPMJSP2155"],"award-info":[{"award-number":["JPMJSP2155"]}]},{"name":"JSPS Grants-in-Aid for Scientific Research (KAKENHI)","award":["JP22bm0804027"],"award-info":[{"award-number":["JP22bm0804027"]}]},{"name":"JST SPRING","award":["23H02876"],"award-info":[{"award-number":["23H02876"]}]},{"name":"JST SPRING","award":["JPMJSP2155"],"award-info":[{"award-number":["JPMJSP2155"]}]},{"name":"JST SPRING","award":["JP22bm0804027"],"award-info":[{"award-number":["JP22bm0804027"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23H02876"],"award-info":[{"award-number":["23H02876"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JPMJSP2155"],"award-info":[{"award-number":["JPMJSP2155"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22bm0804027"],"award-info":[{"award-number":["JP22bm0804027"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, caused by a single base substitution in mitochondrial DNA (m.3243A&gt;G), is one of the most common maternally inherited mitochondrial diseases accompanied by neuronal damage due to defects in the oxidative phosphorylation system. There is no established treatment. Our previous study reported a superior restoration of mitochondrial function and bioenergetics in mitochondria-deficient cells using highly purified mesenchymal stem cells (RECs). However, whether such exogenous mitochondrial donation occurs in mitochondrial disease models and whether it plays a role in the recovery of pathological neuronal functions is unknown. Here, utilizing induced pluripotent stem cells (iPSC), we differentiated neurons with impaired mitochondrial function from patients with MELAS. MELAS neurons and RECs\/mesenchymal stem cells (MSCs) were cultured under contact or non-contact conditions. Both RECs and MSCs can donate mitochondria to MELAS neurons, but RECs are more excellent than MSCs for mitochondrial transfer in both systems. In addition, REC-mediated mitochondrial transfer significantly restored mitochondrial function, including mitochondrial membrane potential, ATP\/ROS production, intracellular calcium storage, and oxygen consumption rate. Moreover, mitochondrial function was maintained for at least three weeks. Thus, REC-donated exogenous mitochondria might offer a potential therapeutic strategy for treating neurological dysfunction in MELAS.<\/jats:p>","DOI":"10.3390\/ijms242417186","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T06:01:07Z","timestamp":1701842467000},"page":"17186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC)"],"prefix":"10.3390","volume":"24","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Center for Genomic and Regenerative Medicine, School of Medicine, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4452-9248","authenticated-orcid":false,"given":"Yasuaki","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2523-545X","authenticated-orcid":false,"given":"Tsukimi","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"},{"name":"Clinical Laboratory Division, Shimane University Hospital, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kawashima-Sonoyama","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaya","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wado","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"Center for Genomic and Regenerative Medicine, School of Medicine, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1731-9793","authenticated-orcid":false,"given":"Masashi","family":"Fujitani","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3257-1305","authenticated-orcid":false,"given":"Takeshi","family":"Taketani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. 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