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Application of IRF1 (Interferon Regulating Factor 1) in regulating and controlling immune regulation effect of mesenchymal stem cells and product

A technology of mesenchymal stem cells and immune regulation, applied in the biological field, can solve problems such as unclear plasticity mechanism

Active Publication Date: 2022-01-28
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some studies have also found that the immunomodulatory properties of MSCs pretreated with serum and inflammatory factors IFN-γ and TNF-a in GVHD patients are enhanced, which can effectively reduce the inflammatory response of GVHD. This phenomenon is called the plasticity of MSC immune regulation, but this plasticity mechanism is still unclear. clear

Method used

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  • Application of IRF1 (Interferon Regulating Factor 1) in regulating and controlling immune regulation effect of mesenchymal stem cells and product
  • Application of IRF1 (Interferon Regulating Factor 1) in regulating and controlling immune regulation effect of mesenchymal stem cells and product
  • Application of IRF1 (Interferon Regulating Factor 1) in regulating and controlling immune regulation effect of mesenchymal stem cells and product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1 Inflammatory factor IFN-γ combined with TNF-α stimulates MSCs to highly express IRF1

[0028] The inflammatory factor IFN-γ combined with TNF-α (20ng / ml) pretreated the isolated and cultured umbilical cord (hu-MSC), placenta (hp-MSC), and amniotic membrane (hm-MSC) MSCs for 12 hours, and established single cells using the 10x Genomics platform Transcriptome library, the mRNA expression of IRF1 in MSC and s-MSC (inflammatory factor stimulation group) was analyzed at the single-cell level, and the results showed that umbilical cord, placenta, and amniotic MSC under the inflammatory microenvironment highly expressed IRF1 ( figure 1 ).

Embodiment 2

[0029] Example 2 Analysis of target gene network regulated by transcription factor IRF1 based on single-cell sequencing

[0030] Based on three MSC single-cell transcriptome libraries of umbilical cord, placenta, and amniotic membrane, SCENIC software can identify the co-expressed modules (regulon) between transcription factors (TFs) and potential target genes and the regulon activity score (regulon activity score) of each cell , RAS), the results showed that IRF1 can regulate the expression of MSC immunosuppressive related genes STAT1, IDO1, CD274 and chemokines CXCL9, CXCL10, suggesting that IRF1 can affect the MSC immunosuppressive properties ( figure 2 ).

Embodiment 3

[0031] Example 3 Molecular level verification that IRF1 regulates the expression of STAT1, IDO1, CD274 and chemokines CXCL9 and CXCL10

[0032] Umbilical cord MSCs were inoculated into 6-well plates (1×10 5 / well), cultured for 24 hours, and when the cell density was about 70%, the transfection reagent jetPRIME (polyplus) was used to transiently transfect siRNA into umbilical cord MSCs for knocking down the expression of IRF1. The sequence of siR-IRF1 is shown in Table 1 (Beijing Sangong). A total of three siR-IRF1s were constructed, and 1110 with the highest knockdown efficiency was selected for subsequent experiments. The transfection system is: buffer 120 μL, jetPRIME 3 μL, siR-IRF1 or NC 4 μL, add 1.88 ml serum-free a-MEM medium, so that the siRNA concentration is 50 μM, and continue to culture for 6-8 hours to replace the complete medium containing 10% FBS, Continue to cultivate for 24h. IFN-γ combined with TNF-α (20ng / ml) pretreated each group of cells after transfect...

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Abstract

The invention discloses an application of an Interferon Regulating Factor 1 (IRF1) in regulating and controlling the immunomodulatory effect of human placenta, amnion and umbilical cord derived mesenchymal stem cells. The immunomodulatory effect is the effect of inhibiting T cell proliferation. The biological characteristics of human amniotic membrane, placenta and umbilical cord derived mesenchymal stem cells are researched by utilizing a single cell sequencing technology, and the IRF1 is found to be highly expressed in the placenta, amniotic membrane and umbilical cord derived mesenchymal stem cells in an inflammatory microenvironment. Transcription factor analysis and in-vitro experimental research further prove that the IRF1 can regulate and control the expression of MSC immunosuppressive molecules IDO1, CD274 and STAT1 and chemotactic factors CXCL9 and CXCL10, and in-vitro T cell proliferation experiments find that the IRF1 can regulate and control the T cell proliferation inhibition effect of the umbilical cord MSC, so that an important theoretical basis and a therapeutic target are provided for treatment of autoimmune diseases.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to research on the mechanism of immune regulation of mesenchymal stem cells. Background technique [0002] Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are mesoderm-derived adult stem cells with multi-directional differentiation potential, which can be differentiated into osteoblasts, cartilage and adipocytes, and skin cells under the influence of various regulatory networks in different microenvironments Wait. The low immunogenicity and strong immunoregulatory properties of mesenchymal stem cells make them widely used in the clinical treatment of autoimmune diseases and important reasons for injury repair. Current studies believe that MSCs transplanted into the body can inhibit the inflammatory response of autoimmune diseases such as type I diabetes, acute graft-versus-host disease, and Crohn's disease, and promote damage repair to treat these inflammatory diseases. [0003]...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0775C07K14/47C12N15/87C12N5/10C12Q1/6851A61K35/28A61K38/19A61K38/21A61K45/00A61P29/00A61P37/02
CPCC12N5/0668C07K14/47C12N15/87C12Q1/6851A61K45/00A61K38/191A61K38/217A61P37/02A61K35/28A61P29/00C12N2501/24C12N2501/25C12N2510/00C12Q2561/113C12Q2563/107C12Q2531/113
Inventor 张毅刘伟江李雪王洋白海涛袁福临刘元林
Owner ACADEMY OF MILITARY MEDICAL SCI
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