Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19

Yinpeng Jin; Junyi Wang; Hongchao Li; Shane Gao; Rongfeng Shi; Danjing Yang; Xianli Wang; Xi Wang; Liang Zhu; Xiaojin Wang; Chengwei Chen; Ke Ning; Zhengliang Gao; Jun Xu; Qingchun Fu

doi:10.1016/j.ebiom.2018.07.015

Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19

EBioMedicine. 2018 Aug:34:231-242. doi: 10.1016/j.ebiom.2018.07.015. Epub 2018 Aug 2.

Authors

Yinpeng Jin¹, Junyi Wang², Hongchao Li², Shane Gao³, Rongfeng Shi⁴, Danjing Yang³, Xianli Wang⁵, Xi Wang⁶, Liang Zhu³, Xiaojin Wang², Chengwei Chen², Ke Ning⁷, Zhengliang Gao⁸, Jun Xu⁹, Qingchun Fu¹⁰

Affiliations

¹ Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China. Electronic address: [email protected].
² Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China.
³ East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.
⁴ Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China.
⁵ Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China.
⁶ Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China.
⁷ Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
⁸ East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China. Electronic address: [email protected].
⁹ East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China. Electronic address: [email protected].
¹⁰ Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China. Electronic address: [email protected].

Abstract

It has previously been reported that human adipose-derived stem cells (hASCs) can promote the regeneration of damaged tissues in rats with liver failure through a 'paracrine effect'. Here we demonstrate a therapeutic effect of hASCs derived Extracellular Vesicles (EVs) on rat models with acute liver failure, as shown by the improvement of the survival rate by >70% compared to controls. Gene sequencing of rat liver revealed an increase in human long-chain non-coding RNA (lncRNA) H19 after hASC-derived EVs transplantation. When the H19 coding sequence was silenced in hASCs and EVs were then collected for treatment of rats with liver failure, we saw a decrease in the survival rate to 40%, compared to treatment with EVs generated from non-silenced hASCs. These data indicate that lncRNA H19 may be a potential therapeutic target for the treatment of liver failure.

Keywords: Adipose-derived stem cells; Extracellular vesicles; Liver failure; LncRNA; Regeneration.

MeSH terms

Adipose Tissue / cytology
Animals
Extracellular Vesicles / transplantation*
Humans
Liver Failure, Acute / metabolism
Liver Failure, Acute / therapy*
Male
RNA, Long Noncoding / administration & dosage*
Rats, Sprague-Dawley
Regeneration
Stem Cells / metabolism

Substances

H19 long non-coding RNA
RNA, Long Noncoding