New achievements in stem cell research of the Chinese Academy of Sciences

Researchers from the Shanghai Institutes for Biological Sciences and the Institute of Health Sciences of Shanghai Jiaotong University School of Medicine have confirmed in mice that mesenchymal stem cells can alleviate bacterial-induced liver damage by inducing regulatory dendritic cells. Related papers were published in the internationally renowned liver disease journal Hepatology (the latest impact factor 11.665).

Researchers Yanyun Zhang and Dr. Bing Wan from the Institute of Health Sciences are co-corresponding authors of this paper. Researcher Zhang Yanyun's main research directions include stem cell immunology, tumor immunology and novel immunobiological targeted therapy research.

Fulminant hepatic failure (FHF) refers to patients who have no liver disease before the disease and suddenly have a large number of hepatocyte necrosis or significant abnormal liver function, and hepaticenc ephalopathy (HE) occurs within 8 weeks after the first symptoms appear Kind of syndrome. The symptoms of primary disease include liver disease face, liver palm and spider skin nevus. The manifestations of liver failure are deepened jaundice, persistent low fever, poor appetite, extreme fatigue, irritability, etc .; stubborn hiccups, nausea, vomiting and obvious abdominal distension; there is a clear bleeding tendency. Its clinical features are acute onset, rapid progress, and critical condition. Although there are many treatments at present, the prognosis of FHF patients is greatly improved, but the mortality rate is still above 50%.

Mesenchymal stem cells (MSCs) are a kind of tissue stem cells with multi-directional differentiation potential widely existing in the body, which are derived from early mesoderm and ectoderm. Mesenchymal stem cells were originally found in the bone marrow, with the characteristics of multi-directional differentiation, hematopoietic support and promotion of stem cell implantation, immune regulation and self-replication. In recent years, animal experiments and some non-random clinical trials have confirmed the efficacy of human bone marrow mesenchymal stem cell (hBMSC) transplantation in the treatment of acute and chronic liver injury, so it is regarded as a very potential treatment for fulminant liver failure.

In this new article, the researchers used Propionibacterium acnes-sensitized, lipopolysaccharide (LPS) -induced liver injury mice as a model of human fulminant liver failure. They confirmed that administration of MSCs can significantly improve liver failure and increase the survival rate of model mice. Allogeneic MSCs and autologous MSCs showed similar effects on fulminant liver failure. MSCs treatment reduced the infiltration and activation of CD4 + T cells in the liver, suppressed Th1 cells, and induced regulatory T (Tregs) cells.

In addition, the researchers tested that the DNA copy of P. acnes in the liver of mice treated with MSC was reduced. Interestingly, the researchers found that MSCs induced specific liver CD11c + MHCIIhi CD80lo CD86lo regulatory dendritic cell populations (DCs). Furthermore, these dendritic cells induced Treg cell differentiation by generating TGF-β. Further mechanistic studies confirmed that during the differentiation of CD11c + B220-dendritic cell precursors into regulatory dendritic cells, MSC-derived prostaglandin E2 and receptor EP4 play a crucial role in a PI3K-dependent manner The role.

These findings confirmed for the first time that MSCs have an important regulatory role in inducing the differentiation of CD11c + B220- dendritic cell precursors into regulatory DCs. The new research reveals a new immune regulation mechanism of MSCs and lays a solid foundation for the application of MSCs in the treatment of fulminant liver failure.

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