2025, Vol. 29 ›› Issue (36): 7848-7855

Epigenetic characteristics of hepatogenic differentiation of mesenchymal stem cells in three-dimensional culture

Huang Haina, Yu Yanrong, Bi Jian, Huang Miao, Peng Weijie   

Abstract: BACKGROUND: Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering. The efficiency of traditional two-dimensional culture for hepatocyte induction is low, and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.
OBJECTIVE: To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells, focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation, providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.
METHODS: Relevant articles in the PubMed and other databases such as CNKI were searched, using Chinese and English search terms “mesenchymal stem cell, 3D culture, hepatogenic differentiation, hepatocyte-like cells, epigenetics.” Additionally, the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.
RESULTS AND CONCLUSION: (1) Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids, biological scaffolds, bioprinting, and microfluidic chips. Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation. (2) During the differentiation of mesenchymal stem cells into hepatocyte-like cells, epigenetic regulation plays a key role, primarily involving histone modification, DNA methylation, and the regulation of non-coding RNAs. (3) Under three-dimensional culture conditions, epigenetic modifications, especially histone acetylation, play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

Key words: mesenchymal stem cell, three-dimensional culture, hepatogenic induction, hepatocyte-like cell, epigenetics, histone acetylation, review