New mechanism in MSCs alleviating liver fibrosis

The occurrence and development of liver fibrosis (LF) are always accompanied by inflammatory responses and the involvement of various immune cells. Anti-inflammatory and immunomodulatory treatments hold promise as new strategies for combating liver fibrosis. Mesenchymal stem cells (MSCs) are a type of pluripotent stem cell with advantages such as multipotent differentiation potential in vitro, low immunogenicity, and immunomodulatory functions. Consequently, MSC-based cell immunotherapy targeting immune dysregulation in the pathological progression of LF is gaining attention and is expected to become a new treatment modality. Currently, numerous studies have demonstrated that MSCs exhibit immunomodulatory effects on various immune cells, such as monocytes, macrophages, dendritic cells, and T cells. However, the regulatory role of MSCs on hepatic B cells in the context of LF and the impact of this regulation on the pathological progression of LF remain unclear.

On March 28, 2024, Professor CAO Hongcui from the State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases of the First Affiliated Hospital, Zhejiang University School of Medicine published an original research paper titled Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells online in Hepatology, the official journal of the American Association for the Study of Liver Diseases. This study found that intrahepatic B cells can serve as targets for MSCs, playing a crucial role in the treatment of liver fibrosis with MSCs. This provides new insights into the mechanisms of action of MSCs.

In this work, the researchers evaluate the effectiveness of MSC transplantation in treating LF by constructing mice models. It was found that MSC transplantation significantly reduced the degree of liver fibrosis. Further research using flow cytometry and single-cell transcriptome sequencing techniques to analyze B cells in fibrotic livers and post-MSC treatment revealed that MSCs inhibit B cell infiltration and phenotypic activation during LF progression. Subsequently, the role of B cells in liver fibrosis progression was confirmed through B cell-deficient mouse models and B cell adoptive transfer models, demonstrating that B cells can serve as target cells for MSC therapy. Finally, in vitro cell experiments explored the mechanisms by which MSCs regulate B cells. The study found that MSCs could inhibit the proliferation, cell cycle progression, and pro-inflammatory cytokine expression of intrahepatic B cells in a non-contact manner. Further exploration revealed that exosomes secreted by MSCs directly participated in the inhibition of intrahepatic B cells, primarily targeting the MAPK and NF-κB signaling pathways.

In summary, this study not only demonstrates the efficacy of MSC transplantation in alleviating liver fibrosis but also highlights the crucial role of B cells in this process and their potential as targets for MSC therapy. The study also provides detailed insights into the specific mechanisms by which MSCs regulate B cells.

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More information: Prof. CAO hongcui is the corresponding author of this article. Ph.D. student FENG Xudong is the first author of this article. Prof. LI Lanjuan contributes to study supervision. This work was supported by National Key Research and Development Program of China (No. 2020YFA0113003), Key Research, Development Project of Zhejiang Province (No. 2023C03046), and Fundamental Research Funds for the Central Universities (No. 2022ZFJH003).

Source: The First Affiliated Hospital, Zhejiang University School of Medicine