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Wnt5a-knock-down M1 type bone marrow-derived macrophage for treating hepatic fibrosis and liver cirrhosis and application of M1 type bone marrow-derived macrophage

A bone marrow-derived, macrophage technology, applied in the field of cell biology and liver disease prevention and treatment, to inhibit the progress of liver cirrhosis, reduce the inflammatory response of the liver, and promote the progress.

Pending Publication Date: 2022-02-08
SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there is no report on the use of Wnt5a knockdown M1 bone marrow-derived macrophages in the treatment of liver fibrosis and cirrhosis.

Method used

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  • Wnt5a-knock-down M1 type bone marrow-derived macrophage for treating hepatic fibrosis and liver cirrhosis and application of M1 type bone marrow-derived macrophage
  • Wnt5a-knock-down M1 type bone marrow-derived macrophage for treating hepatic fibrosis and liver cirrhosis and application of M1 type bone marrow-derived macrophage
  • Wnt5a-knock-down M1 type bone marrow-derived macrophage for treating hepatic fibrosis and liver cirrhosis and application of M1 type bone marrow-derived macrophage

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Effect test

Embodiment 1

[0029] Using carbon tetrachloride / 2-acetamidofluorene (CCl 4 / 2-AAF)-induced rat liver cirrhosis model confirmed that the Wnt5a knockdown M1 type bone marrow-derived macrophages of the present invention play an important role in inhibiting the progression of liver cirrhosis.

[0030] 1. Establishment of rat bone marrow-derived macrophage M1 subtype Wnt5a knockdown or overexpression model

[0031] 1.1 Materials

[0032] 1.1.1 Animals

[0033] Five SD male rats, clean grade, weighing 80-100 g, were used to isolate BMSCs and were purchased from Beijing Weitong Lihua Experimental Animal Co., Ltd., license number: SCXK (Shanghai) 2013-0016.

[0034] 1.1.2 Main reagents

[0035] Growth factors: GM-CSF was purchased from Cyagen; M-CSF was purchased from Novus Biologicals. The L929 cell line was purchased from the Cell Bank of the Chinese Academy of Sciences. Rabbit polyclonal antibody anti-CD11b / c [Alexa ] (NB110-40766AF405), mouse monoclonal antibody anti-CD68 [Alexa ] (NB100...

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Abstract

The invention provides a Wnt5a-knock-down M1 type bone marrow-derived macrophage for treating hepatic fibrosis and liver cirrhosis and application of the M1 type bone marrow-derived macrophage. According to the invention, a CCl4 / 2-AAF rat liver cirrhosis model is established, and it is found that the anti-hepatic fibrosis effect of the M1 type bone marrow macrophage, in which a non-classical Wnt signal channel ligand, namely a Wnt5a gene is knocked down, can be remarkably improved after peripheral intravenous injection, and the remarkably improved anti-hepatic fibrosis effect is mainly manifested in that liver inflammatory response is remarkably relieved, hepatic stellate cell activation is inhibited, differentiation of hepatic progenitor cells to bile duct epithelial cells (a bile duct reaction) is inhibited, further hepatic fibrosis is inhibited, and then liver cirrhosis progress is inhibited. On the contrary, after a Wnt5a-gene-overexpressed M1 type bone marrow macrophage is injected, the progress of liver cirrhosis is obviously promoted. Therefore, the M1 type bone marrow macrophage in which the Wnt5a gene is knocked down can be used as an innovative biological or chemical treatment medicine for hepatic fibrosis and cirrhosis.

Description

technical field [0001] The invention belongs to the fields of cell biology and prevention and treatment of liver diseases, and in particular relates to a Wnt5a knockdown M1 type bone marrow-derived macrophage for treating liver fibrosis and liver cirrhosis and its application. Background technique [0002] Liver cirrhosis is the late stage of various chronic liver diseases. Once it develops to the decompensated stage, liver transplantation is recognized as an effective treatment, but it is limited by the lack of donors and high cost, making it lack of universality. Therefore, it is particularly urgent to promote the reconstruction of the diseased liver's own structure. [0003] Macrophages are highly plastic, allowing them to rapidly switch between pro-inflammatory and anti-inflammatory phenotypes in response to environmental cues. Under the influence of bacterial lipopolysaccharide (LPS) or cytokines produced by injury or inflammation, macrophages can undergo classical act...

Claims

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Application Information

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IPC IPC(8): C12N5/10C12N15/867C12N15/12A61K35/15A61P1/16
CPCC12N5/0645C12N15/86C07K14/475A61K35/15A61P1/16C12N2510/00C12N2740/15043C12N2800/107
Inventor 慕永平王丹阳许燕楠刘平陈佳美刘伟陈高峰张华
Owner SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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