Mitochondrial transfer from Wharton's jelly-derived mesenchymal stem cells to mitochondria-defective cells recaptures impaired mitochondrial function

被引:96
作者
Lin, Hung-Yu [1 ,2 ,3 ,4 ,8 ,12 ]
Liou, Chia-Wei [2 ,3 ,4 ,8 ]
Chen, Shang-Der [2 ,3 ,4 ,8 ,12 ]
Hsu, Te-Yao [3 ,5 ]
Chuang, Jiin-Haur [3 ,4 ,6 ]
Wang, Pei-Wen [3 ,4 ,7 ]
Huang, Sheng-Teng [3 ,4 ,9 ]
Tiao, Mao-Meng [3 ,4 ,10 ]
Chen, Jin-Bor [3 ,4 ,11 ]
Lin, Tsu-Kung [2 ,3 ,4 ,8 ]
Chuang, Yao-Chung [1 ,2 ,3 ,8 ]
机构
[1] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan
[2] Kaohsiung Chang Gung Mem Hosp, Dept Neurol, Kaohsiung 833, Taiwan
[3] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan
[4] Kaohsiung Chang Gung Mem Hosp, Mitochondrial Res Unit, Kaohsiung 833, Taiwan
[5] Kaohsiung Chang Gung Mem Hosp, Dept Obstet & Gynecol, Kaohsiung 833, Taiwan
[6] Kaohsiung Chang Gung Mem Hosp, Div Pediat Surg, Kaohsiung 833, Taiwan
[7] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Kaohsiung 833, Taiwan
[8] Kaohsiung Chang Gung Mem Hosp, Ctr Parkinsons Dis, Kaohsiung 833, Taiwan
[9] Kaohsiung Chang Gung Mem Hosp, Dept Chinese Med, Kaohsiung 833, Taiwan
[10] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan
[11] Kaohsiung Chang Gung Mem Hosp, Dept Nephrol, Kaohsiung 833, Taiwan
[12] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan
关键词
Wharton's jelly mesenchymal stem cell; Mitochondrial transfer; Mitochondrial dysfunction; HUMAN UMBILICAL-CORD; BONE-MARROW; IN-VITRO; PHENOTYPIC CHARACTERIZATION; ENERGY-METABOLISM; ADIPOSE-TISSUE; STROMAL CELLS; DIFFERENTIATION; CARDIOMYOCYTES; RESPIRATION;
D O I
10.1016/j.mito.2015.02.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Adult mesenchymal stem cell (MSC)-conducted mitochondrial transfer has been recently shown to rescue cellular bioenergetics and prevent cell death caused by mitochondrial dysfunction. Wharton's jelly-derived MSCs (WJMSCs) harvested from postpartum umbilical cords are an accessible and abundant source of stem cells. This study aimed to determine the capability of WJMSCs to transfer their own mitochondria and rescue impaired oxidative phosphorylation (OXPHOS) and bioenergetics caused by mitochondrial DNA defects. To do this, WJMSCs were co-cultured with mitochondrial DNA (mtDNA)-depleted rho(0) cells and the recapture of mitochondrial function was evaluated. WJMSCs were shown to be capable of transferring their own mitochondria into rho(0) cells and underwent interorganellar mixture within these cells. Permissive culture media (BrdU-containing and pyruvate- and uridine-free) sieved out a survival cell population from the co-cultured WJMSCs (BrdU-sensitive) and rho(0) cells (pyruvate/uridine-free). The survival cells had mtDNA identical to that of WJMSCs, whereas they expressed cellular markers identical to that of rho(0) cells. Importantly, these rho(0)-plus -WJMSC-mtDNA (rho(+w)) cells recovered the expression of mtDNA-encoded proteins and exhibited functional oxygen consumption and respiratory control, as well as the activity of electron transport chain (ETC) complexes I, II, III and IV. In addition, ETC complex V-inhibitor-sensitive ATP production and metabolic shifting were also recovered. Furthermore, cellular behaviors including attachment-free proliferation, aerobic viability and OXPHOS-reliant cellular motility were also regained after mitochondrial transfer by WJMSCs. The therapeutic effect of WJMSCs-derived mitochondrial transfer was able to stably sustain for at least 45 passages. In conclusion, this study suggests that WJMSCs may serve as a potential therapeutic strategy for diseases linked to mitochondrial dysfunction through the donation of healthy mitochondria to cells with genetic mitochondrial defects. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
引用
收藏
页码:31 / 44
页数:14
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