Application of Hnf-1alpha gene modified mesenchymal stem cells in prevention and treatment of liver cancer

A kind of high-quality stem cell technology, which is applied in the field of stem cell therapy to prevent the recurrence and metastasis of liver cancer in the early stage, and can solve the problems of damage and secondary trauma of patients

Pending Publication Date: 2022-07-08
中国人民解放军海军军医大学第三附属医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although the above-mentioned traditional treatment schemes may have improved the patient's survival rate and quality of life to a certain ex

Method used

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  • Application of Hnf-1alpha gene modified mesenchymal stem cells in prevention and treatment of liver cancer
  • Application of Hnf-1alpha gene modified mesenchymal stem cells in prevention and treatment of liver cancer
  • Application of Hnf-1alpha gene modified mesenchymal stem cells in prevention and treatment of liver cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Example 1. Isolation and identification of rat bone marrow primary mesenchymal stem cells and preparation of Hnf-1α overexpressing mesenchymal stem cells

[0090] In this example, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were used as an example to study.

[0091] (1) Isolation and in vitro culture of rat bone marrow mesenchymal stem cells

[0092] Bone marrow MSCs were isolated and cultured in vitro from SD rats by adherent culture method. Male SD rats 200-250 g were taken, anesthetized with 10% chloral hydrate, and the femur was removed and placed in L-DMEM medium after routine disinfection. In the ultra-clean bench, rinse the bone marrow cavity with L-DMEM medium, collect the bone marrow suspension, centrifuge for 5 minutes (1500 rpm), discard the supernatant, collect the cell pellet, add L-DMEM+10% fetal bovine serum+ 100U / mL penicillin + 100U / mL streptomycin, counted by hemocytometer, 1×10 5 / cm 2 Inoculated in a 10cm petri dish, in L-DMEM+10% fet...

Embodiment 2

[0108] Example 2. Study on the effect of Hnf-1α gene-modified MSCs on the occurrence and development of DEN-induced primary liver cancer in rats

[0109] After adaptive feeding for one week, 20 SD rats were randomly divided into 4 groups with 5 rats in each group, namely PBS infusion group (Ctrl), Ad-GFP-MSCs infusion group (Ad-GFP-MSCs), Ad-Hnf -1α-MSCs infusion group (Ad-Hnf-1α-MSCs) and Ad-Hnf-1α infusion group, experimental animals in all treatment groups were fed DEN water (0.1% diethylnitrosamine), and animals in each experimental group were fed with DEN water (0.1% diethylnitrosamine). Tail vein injection started from the 4th week of DEN induction (early stage of cancer induction, or called mutation stage), 1.5×10 6 cells / only / 800μL; the control group (Ctrl) was infused with 800μL of PBS; the tail vein was injected once every two weeks, three times in total. Then continue to feed DEN water until the end of 14 weeks, and change to ordinary drinking water. The survival ...

Embodiment 3

[0112] Example 3. Effect of Hnf-1α gene-modified mesenchymal stem cells on DEN-induced liver injury repair

[0113] After 15 SD rats were adaptively fed for one week, they were randomly divided into 3 groups with 5 rats in each group, namely PBS infusion group (Ctrl), Ad-GFP-MSCs infusion group (Ad-GFP-MSCs) and Ad-Hnf In the -1α-MSCs infusion group (Ad-Hnf-1α-MSCs), all the experimental animals in the treatment groups were fed DEN water (0.1% diethylnitrosamine). Tail vein injection, 1.5 x 10 6 cells / only / 800μL; the control group was infused with 800μL of PBS; the tail vein was injected once every two weeks, three times in total. At the 8th week of DEN treatment, the experimental animals were sacrificed, and the animal serum and liver tissue were collected for relevant detection.

[0114] The results of biochemical analysis showed that compared with the Ctrl control group, the levels of liver function indexes such as ALT, AST, TBIL and DBIL in the serum of the animals in th...

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Abstract

The invention provides an application of a mesenchymal stem cell modified by a hepatocyte nuclear factor-1 alpha (Hnf-1 alpha) gene in prevention and treatment of diseases such as liver cancer and the like, and particularly provides a mesenchymal stem cell modified by a hepatocyte nuclear factor-1 alpha (Hnf-1 alpha) gene and a preparation method of the mesenchymal stem cell modified by the hepatocyte nuclear factor-1 alpha (Hnf-1 alpha) gene. The modified cell disclosed by the invention has the effects of inhibiting liver cancer, inhibiting hepatic fibrosis, repairing liver injury and/or inhibiting inflammation; the inhibition comprises prevention or treatment. The invention provides a new clinical treatment approach for preventing and treating diseases such as liver cancer, is expected to be used for preventing and treating liver cancer postoperative recurrence of liver cancer patients, and has a good development prospect.

Description

technical field [0001] The present invention belongs to the field of biotechnology; more specifically, the present invention relates to the use of Hnf-1α gene-modified mesenchymal stem cells in preventing and treating liver diseases such as liver cancer, and particularly provides a stem cell treatment scheme for preventing early postoperative recurrence and metastasis of liver cancer. Background technique [0002] Cancer is still a disease that is difficult for humans to overcome. With advances in medicine, although there has been some success using surgery, chemotherapy and radiation to cure cancer, new strategies are still needed. [0003] Primary hepatocellular carcinoma (PHC) is the fifth most common malignant tumor and the third leading cause of cancer death in the world. The number of new liver cancer cases in the world is about 550,000 every year, and its incidence has been increasing in recent years. . China is the "hardest hit area" for liver cancer, with about 20...

Claims

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Application Information

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IPC IPC(8): A61K35/28A61K35/50A61K35/51A61P35/00C12N5/10C12N15/12C12N15/861
CPCA61K35/28A61K35/51A61K35/50A61P35/00C07K14/4702C12N15/86C12N2710/10043
Inventor 卫立辛宗晨韩志鹏杨雪叶菲
Owner 中国人民解放军海军军医大学第三附属医院
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