J Korean Med Sci.  2019 Nov;34(45):e273. 10.3346/jkms.2019.34.e273.

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

Affiliations
  • 1Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.
  • 2Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea. sayjunekim@gmail.com
  • 3Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul, Korea.
  • 4Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.

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.

Keyword

Adipose-Derived Stem Cells; Liver Fibrosis; microRNAs; miR-214; Mesenchymal Stem Cells; Secretome
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