Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts
Joint Authors
Lin, Tsu-Kung
Chuang, Jiin-Haur
Liou, Chia-Wei
Chen, Shang-Der
Lan, Min-Yu
Tsai, Meng-Han
Huang, Sheng-Teng
Wang, Xiao-Wen
Tsai, Po-Chin
Wang, Feng-Sheng
Wang, Pei-Wen
Lin, Hung-Yu
Chuang, Yao-Chung
Hsu, Te-Yao
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-22
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Wharton’s jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect.
Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene.
The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria.
We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions.
In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts.
By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated.
After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention.
Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs.
Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance.
This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer.
This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.
American Psychological Association (APA)
Lin, Tsu-Kung& Chen, Shang-Der& Chuang, Yao-Chung& Lan, Min-Yu& Chuang, Jiin-Haur& Wang, Pei-Wen…[et al.]. 2019. Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1206462
Modern Language Association (MLA)
Lin, Tsu-Kung…[et al.]. Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1206462
American Medical Association (AMA)
Lin, Tsu-Kung& Chen, Shang-Der& Chuang, Yao-Chung& Lan, Min-Yu& Chuang, Jiin-Haur& Wang, Pei-Wen…[et al.]. Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1206462
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206462