title: Bone marrow-derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model.
abstract: The transplantation of mesenchymal stem cells (MSCs) is considered to be a promising treatment for ischemic heart disease; however, the therapeutic effects and underlying mechanisms of action require further evaluation. Mitochondrial dysfunction is a key event in simulated ischemia/reperfusion (SI/R) injury. The purpose of the present study was to investigate the mechanism of mitochondrial transfer, which may be involved the antiapoptotic action of co-culture with MSCs. An in vitro model of simulated ischemia/reperfusion (SI/R) was used in the present study. The apoptotic indexes were significantly increased when H9c2 cardiomyocytes were induced in the SI/R group. Following co-culture with bone marrow-derived (BM)-MSCs, H9c2 cells exhibited marked resistance against the SI/R-induced apoptotic process. Besides, mitochondrial transfer via a tunneling nanotube (TNT) like structure was detected by confocal fluorescent microscopy. In addition, following pretreated with latrunculin-A (LatA), an inhibitor of TNT formation, the BM-MSCs were not able to rescue injured H9c2 cells from apoptosis, as previously observed. In conclusion, the anti-apoptotic ability of BM-MSCs may be partially attributed to the recovery of mitochondrial dysfunction in SI/R, and the formation of TNTs appears to be involved in this action of mitochondrial transfer between adjacent cells.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Shanghai 200003, P.R. China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Gynaecology and Obstetrics, Nanjing Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yanjia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jiateng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000637:transplantation*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D043942:Nanotubes / Q000737:chemistry; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*