1. Academic Validation
  2. Human umbilical cord-derived mesenchymal stromal cells alleviate liver cirrhosis through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanism

Human umbilical cord-derived mesenchymal stromal cells alleviate liver cirrhosis through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanism

  • Int Immunopharmacol. 2023 Jul 24;123:110456. doi: 10.1016/j.intimp.2023.110456.
Lichao Yao 1 Xue Hu 1 Mengqin Yuan 1 Pingji Liu 1 Qiuling Zhang 1 Zheng Wang 1 Ping Chen 1 Zhiyu Xiong 1 Lun Wu 2 Kai Dai 3 Yingan Jiang 4
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.
  • 2 Experiment Center of Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan 442008, People's Republic of China. Electronic address: wulun0909@163.com.
  • 3 Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China. Electronic address: daikai@whu.edu.cn.
  • 4 Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China. Electronic address: jiangya_cn@aliyun.com.
Abstract

Background: Few effective anti-fibrotic therapies are currently available for liver cirrhosis. Mesenchymal stromal cells (MSCs) ameliorate liver fibrosis and contribute to liver regeneration after cirrhosis, attracting much attention as a potential therapeutic strategy for the disease. However, the underlying molecular mechanism of their therapeutic effect is still unclear. Here, we investigated the effect of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in treating liver cirrhosis and their underlying mechanisms.

Methods: We used carbon tetrachloride (CCl4)-induced mice as liver cirrhosis models and treated them with hUC-MSCs via tail vein injection. We assessed the changes in liver function, inflammation, and fibrosis by histopathology and serum biochemistry and explored the mechanism of hUC-MSCs by RNA Sequencing (RNA-seq) using liver tissues. In addition, we investigated the effects of hUC-MSCs on hepatic stellate cells (HSC) and macrophages by in vitro co-culture experiments.

Results: We found that hUC-MSCs considerably improved liver function and attenuated liver inflammation and fibrosis in CCl4-injured mice. We also showed that these cells exerted therapeutic effects by regulating the Hippo/YAP/Id1 axis in vivo. Our in vitro experiments demonstrated that hUC-MSCs inhibit HSC activation by regulating the Hippo/YAP signaling pathway and targeting Id1. Moreover, hUC-MSCs also alleviated liver inflammation by promoting the transformation of macrophages to an anti-inflammatory phenotype.

Conclusions: Our study reveals that hUC-MSCs relieve liver cirrhosis in mice through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanisms, providing a theoretical basis for the future use of these cells as a potential therapeutic strategy for patients with liver cirrhosis.

Keywords

Hepatic stellate cells; Hippo/YAP; Human umbilical cord-derived mesenchymal stromal cells; Liver cirrhosis; Macrophages.

Figures
Products
Inhibitors & Agonists
Other Products