miR-10a Delivered via MSC-derived Extracellular Vesicles Modulates Inflammation in a CCl4-induced Liver Fibrosis Model

Liang  Wang; Youjia  Ni

doi:10.18502/ijaai.v25i1.20454

Liang Wang Department of Hepatobiliary Surgery, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China
Youjia Ni Department of Liver Disease, The First Affiliated Hospital of Chongqing University of Chinese Medicine/Chongqing Traditional Chinese Medicine Hospital, Chongqing, China

DOI: https://doi.org/10.18502/ijaai.v25i1.20454

Keywords: Cytokine; Extracellular vesicle; Mesenchymal stem cells

Abstract

Liver fibrosis is a significant global health issue characterized by an abnormal accumulation of extracellular matrix proteins, that disrupts normal liver architecture and function. Mesenchymal stem cells (MSCs) show therapeutic potential by releasing extracellular vesicles (EVs) containing regulatory microRNAs like miR-10a.

This study evaluates miR-10a-enriched human umbilical cord MSC (hUCMSC)-EVs in a CCl₄-induced model of liver fibrosis, focusing on inflammatory marker modulation. Liver fibrosis was induced in experimental animals using CCl₄ administration. MSCs were isolated from the human umbilical cord and loaded with either a miR-10a mimic or a control sequence through Lipofectamine 3000. EVs were then isolated from the culture media of both miR-control and miR-10a-modified MSCs. The therapeutic potential of these miR-10a-loaded EVs was assessed by treating the CCl₄-induced fibrosis model with these vesicles. The efficacy of the treatment was evaluated by measuring two anti-inflammatory markers interleukin (IL)-10 and IL-4) and three pro-inflammatory markers (tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ)) using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) techniques.

The administration of miR-10a-loaded MSC-EVs resulted in a significant modulation of inflammatory markers. Our results revealed an increase in the levels of anti-inflammatory cytokines (IL-10 and IL-4) and a concurrent decrease in pro-inflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the treated group compared to the control group.

The study demonstrates the therapeutic potential of MSC-EVs encapsulating miR-10a in ameliorating CCl₄-induced liver fibrosis. By modulating the balance between pro-inflammatory and anti-inflammatory cytokines, miR-10a-loaded EVs show promise as a targeted treatment approach for liver fibrosis.