A method for converting mature right ventricular cardiomyocytes into immature cardiomyocytes

A technique of cardiomyocytes and right ventricle, applied in the biological field

Active Publication Date: 2022-06-24
SHANGHAI CHILDRENS MEDICAL CENT AFFILIATED TO SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, there is no report on the technical scheme of knocking out or down-regulating CBP / p300 to promote the transformation of mature right ventricular cardiomyocytes into immature cardiomyocytes, and then treat heart failure.

Method used

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  • A method for converting mature right ventricular cardiomyocytes into immature cardiomyocytes
  • A method for converting mature right ventricular cardiomyocytes into immature cardiomyocytes
  • A method for converting mature right ventricular cardiomyocytes into immature cardiomyocytes

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Embodiment 1

[0034] 1. Experimental materials

[0035] CBP flox / flox ;p300 flox / flox ;Rosa26 -Trap / trap The mice were donated by Professor William Pu of Harvard Medical School. Also available from Jackson lab: CBP flox Mice, Cat. No.: STOCK NO: 025178 / CBP flox; p300 flox Mice, Cat. No.: STOCK NO: 025526 / p300 flox; CBP flox / + Mice Self-Med to Obtain CBP flox / flox ;p300 + / + mouse; p300 flox / + Mice self-mating can acquire p300 flox / flox ;CBP + / + mice; the CBP flox / flox ;p300 + / + Mice and p300 flox / flox ;CBP + / + Mice mated to get CBP flox / + ;p300 flox / + Mice; then CBP flox / + ;p300 flox / + Mice Self-Mate to Obtain CBP flox / flox ;p300 flox / flox mice.

[0036] AAV-TnT-Cre was purchased from Addgene, catalog number: #69916.

[0037] 2. Experimental method

[0038] During the adulthood of mice (day 28 after birth), a low dose (2.0×10 10 vp / g of AAV-TnT-Cre was subcutaneously injected into CBP flox / flox ;p300flox / flox ;Rosa26 -Trap / trap Mice, specific knockout of histone acet...

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Abstract

The present invention relates to a method for converting mature right ventricular cardiomyocytes into immature cardiomyocytes. The present invention found that after the specific knockout of histone acetyltransferase CBP / p300 in some right ventricular cardiomyocytes of mice, the right ventricular cardiomyocytes transdifferentiated into an immature state (cells became smaller, sarcomere-related gene expression was down-regulated, mature myocardium The expression of cell-specific marker T tubes decreased or disappeared, and the ability of cardiomyocytes to deal with calcium ions was down-regulated), and cardiomyocytes formed multiple proliferation clusters, indicating that the right ventricular mature cardiomyocytes can be transdifferentiated into immature cardiomyocytes by inhibiting CBP / p300, so that It has the ability to proliferate and regenerate. The present invention provides an alternative method for the treatment of right heart failure.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a method for converting mature right ventricle cardiomyocytes into immature cardiomyocytes. Background technique [0002] Congenital heart disease (congenital heart disease for short) refers to the abnormal anatomical structure of the heart caused by the formation disorder or abnormal development of the heart and great blood vessels during the embryonic development period, or the failure of the automatic closing channel after birth (it is normal in the fetus). ) diseases. my country is one of the countries with a high incidence of congenital heart disease in the world. About 300,000 children with congenital heart disease are born every year, ranking first among birth defects. About 80% of them need surgical treatment, which is one of the leading causes of death for children under 5 years old. one. [0003] Congenital heart disease in my country is mainly based on the right heart sys...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P9/04C12N5/10
CPCA61K45/00A61P9/04C12N5/0657C12N9/1029C12Y203/01048C12N2510/00
Inventor 叶霖财洪海筏刘锦纷仇黎生姜川张海波张浩肖颖颖
Owner SHANGHAI CHILDRENS MEDICAL CENT AFFILIATED TO SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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