Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells
10.3346/jkms.2019.34.e273
- Author:
Jung Hyun PARK
1
;
Ok Hee KIM
;
Kee Hwan KIM
;
Ha Eun HONG
;
Haeyeon SEO
;
Ho Joong CHOI
;
Joseph AHN
;
Tae Yun LEE
;
Say June KIM
Author Information
1. Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Adipose-Derived Stem Cells;
Liver Fibrosis;
microRNAs;
miR-214;
Mesenchymal Stem Cells;
Secretome
- MeSH:
Actins;
Animals;
Culture Media, Conditioned;
Humans;
Inflammation;
Infusions, Intravenous;
Liver;
Liver Cirrhosis;
Mesenchymal Stromal Cells;
Mice;
MicroRNAs;
Research Personnel;
Stem Cell Research;
Stem Cells;
Transfection
- From:Journal of Korean Medical Science
2019;34(45):e273-
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Secretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214. METHODS: We generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis. RESULTS: Compared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function. CONCLUSION: MicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.
