Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage.
Recent studies have demonstrated that mesenchymal stem cells (MSCs) can donate mitochondria to airway epithelial cells and rescue mitochondrial damage in lung injury. We sought to determine whether MSCs could donate mitochondria and protect against oxidative stress-induced mitochondrial dysfunction in the cornea. Co-culturing of MSCs and corneal epithelial cells (CECs) indicated that the efficiency of mitochondrial transfer from MSCs to CECs was enhanced by Rotenone (Rot)-induced oxidative stress. The efficient mitochondrial transfer was associated with increased formation of tunneling nanotubes (TNTs) between MSCs and CECs, tubular connections that allowed direct intercellular communication. Separation of MSCs and CECs by a transwell culture system revealed no mitochiondrial transfer from MSCs to CECs and mitochondrial function was impaired when CECs were exposed to Rot challenge. CECs with or without mitochondrial transfer from MSCs displayed a distinct survival capacity and mitochondrial oxygen consumption rate. Mechanistically, increased filopodia outgrowth in CECs for TNT formation was associated with oxidative inflammation-activated NFκB/TNFαip2 signaling pathways that could be attenuated by reactive oxygen species scavenger N-acetylcysteine (NAC) treatment. Furthermore, MSCs grown on a decellularized porcine corneal scaffold were transplanted onto an alkali-injured eye in a rabbit model. Enhanced corneal wound healing was evident following healthy MSC scaffold transplantation. And transferred mitochondria was detected in corneal epithelium. In conclusion, mitochondrial transfer from MSCs provides novel protection for the cornea against oxidative stress-induced mitochondrial damage. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.
Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Dan
D
Jiang
Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Fei
F
Gao
Department of Medicine, The University of Hong Kong, Hong Kong, China.
Yuelin
Y
Zhang
Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
David Sai Hung
DS
Wong
Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Qing
Q
Li
Department of Medicine, The University of Hong Kong, Hong Kong, China.|Shenzhen Institutes of Research and Innovation, University of Hong Kong, Hong Kong, China.
Hung-Fat
HF
Tse
National Engineering Laboratory for Regenerative Medical Implantable Devices, 12 Yuyan Road, Guangzhou, China.
Goufeng
G
Xu
Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Zhendong
Z
Yu
Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, The University of Hong Kong, Hong Kong, China.|Shenzhen Institutes of Research and Innovation, University of Hong Kong, Hong Kong, China.
Qizhou
0000-0001-8189-7160
Q
Lian
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019573:Epithelium, Corneal / Q000473:pathology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D043942:Nanotubes / Q000737:chemistry; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity; D034421:Sus scrofa; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012402:Rotenone