2. Academic Validation
  3. Exosomes From Intestinal Epithelial Cells Promote Hepatic Differentiation of Liver Progenitor Cells in Gut-Liver-on-a-Chip Models

Exosomes From Intestinal Epithelial Cells Promote Hepatic Differentiation of Liver Progenitor Cells in Gut-Liver-on-a-Chip Models

  • Adv Sci (Weinh). 2025 Aug;12(32):e17478. doi: 10.1002/advs.202417478.
Liang Ye 1,  Shi Li 1 2,  Guofang Bi 3,  Binghui Li 1 2,  Zhai Cai 4,  Meixian Jin 5,  Ying Zhang 2,  Wanren Yang 1 2,  Yang Li 1,  Shao Li 1,  Wei Hu 6,  Yi Gao 1,  Mingxin Pan 1,  Shuqin Zhou 5 6,  Chao Zhang 7,  Huichang Bi 3,  Qing Peng 2 8
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery II, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.
  • 2 Central Laboratory of the Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 510282, China.
  • 3 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510282, China.
  • 4 Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510000, China.
  • 5 Anesthesiology Department of the Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 518172, China.
  • 6 Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
  • 7 Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
  • 8 Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
PMID: 40619613 DOI: 10.1002/advs.202417478
Abstract

Hepatic progenitor cells (HPCs) are frequently overactivated, and their differentiation into hepatocytes is impaired in advanced liver diseases. To explore the effects of intestinal epithelial cells and their exosomes on the hepatic differentiation of HPCs, co-culture systems of Caco-2/HepaRG cell lines and intestine/HPC organoids are established in a novel gut-liver-on-a-chip. Exosomes derived from intestinal organoids are administered to mice with carbon tetrachloride (CCL4)-induced liver fibrosis. The results showed that the co-culture of HPCs and intestinal epithelial cells promoted the hepatic differentiation of HPCs, mediated by exosomes derived from intestinal epithelial cells. Treatment with exosomes derived from intestinal organoids ameliorated liver fibrosis in a mouse model of CCL4-induced liver fibrosis. A cluster of miRNAs, miR-371-373, is identified within the exosomes of the intestinal epithelial cells, which target RPS6KA2 to modulate hepatic differentiation. This findings demonstrate that exosomes from intestinal epithelial cells promote the hepatic differentiation of HPCs. Exosomes from intestinal organoids may be a novel therapeutic strategy for the treatment of advanced liver diseases.

Keywords

exosomes; hepatic progenitor cells; intestinal epithelial cells; liver fibrosis; organ‐on‐a‐chip.

Figures
Products