Mitochondrial Transfer from Wharton's Jelly Mesenchymal Stem Cell to MERRF Cybrid Reduces Oxidative Stress and Improves Mitochondrial Bioenergetics.

Abstract

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria. The MERRF cybrid cells exhibited a high mt.8344A>G mutation ratio, enhanced ROS level and oxidative damage, impaired mitochondrial bioenergetics, defected mitochondria-dependent viability, exhibited an imbalance of mitochondrial dynamics, and are susceptible to apoptotic stress. Coculture experiments revealed that mitochondria were intercellularly conducted from the WJMSC to the MERRF cybrid. Furthermore, WJMSC transferred mitochondria exclusively to cells with defective mitochondria but not to cells with normal mitochondria. MERRF cybrid following WJMSC coculture (MF+WJ) demonstrated improvement of mt.8344A>G mutation ratio, ROS level, oxidative damage, mitochondrial bioenergetics, mitochondria-dependent viability, balance of mitochondrial dynamics, and resistance against apoptotic stress. WJMSC-derived mitochondrial transfer and its therapeutic effect were noted to be blocked by F-actin depolymerizing agent cytochalasin B. Collectively, the WJMSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction.

• Authors: Yao-Chung Chuang, Chia-Wei Liou, Shang-Der Chen, Pei-Wen Wang, Jiin-Haur Chuang, Mao-Meng Tiao, Te-Yao Hsu, Hung-Yu Lin, Tsu-Kung Lin
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2017 Pg. 5691215 ( 2017) ISSN: 1942-0994 [Electronic] United States
• PMID: 28607632 (Publication Type: Journal Article)

Topics

• Cells, Cultured
• Energy Metabolism
• Humans
• MERRF Syndrome (genetics)
• Mesenchymal Stem Cells (metabolism)
• Mitochondria (metabolism)
• Wharton Jelly