Artificial liver organ and preparation method and application thereof

A technology of organoids and livers, applied in biochemical equipment and methods, artificial cell constructs, 3D culture, etc., can solve the problems of scarcity of liver disse gap organoids, low production efficiency of organoids, affecting nutrient and oxygen supply, etc., to achieve The manufacturing process can be standardized, the microstructure efficiency and repeatability are high, and the effect of imitation repeatability can be satisfied

Pending Publication Date: 2021-11-30
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are many reports on the construction of liver organoids based on liver stem cells, mesenchymal stem cells, endothelial cells, hepatic cell lines, hepatic stellate cell lines, embryonic stem cells, and induced pluripotent stem cells, but liver Disse gap organoid

Method used

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  • Artificial liver organ and preparation method and application thereof
  • Artificial liver organ and preparation method and application thereof
  • Artificial liver organ and preparation method and application thereof

Examples

Experimental program
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Embodiment 1

[0070] Example 1 Using electrostatic bioprinting technology to engineer and prepare hydrogel 3D structures containing various cells

[0071] This embodiment provides a method for preparing artificial liver organoids (such as figure 1 As shown, wherein 1 is a hepatic parenchymal cell, 2 is a hydrogel material, 3 is an endothelial cell, and 4 is a process of a hepatic stellate cell), as follows:

[0072] 1. Directed differentiation of induced pluripotent stem cells (iPSCs) into hepatic parenchymal cells

[0073] (1) Cell differentiation:

[0074] Culture iPSC (ATCC) to induce differentiation when the cell confluency reaches 80%;

[0075] First use induction medium 1 to culture for 3-5 days, the components include DMEM-F12 (Thermo Fisher), 1×B27 (Gibco), 50ng / mL Activin A (R&D, 338-AC), and restricted endoderm can be obtained at this stage cell.

[0076] Next, use induction medium 2 to culture for 4-8 days. The components include DMEM-F12 (Thermo Fisher), B27 (Gibco), 200ng / m...

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Abstract

The invention relates to the field of biological materials and biomedical engineering, and particularly relates to an artificial liver organ and a preparation method and application thereof. The artificial liver organ comprises an endothelial cell layer, a hepatic stellate cell layer and a hepatic parenchyma cell layer; the different cell layers are arranged in a bionic and close mode, and the distance between different kinds of adjacent cells is smaller than 30 micrometers; the mechanical property of the artificial liver organ is 500Pa-1MPa; and the characteristic length of the artificial liver organ is 50-1000 micrometers. The constructed liver organ comprises liver cells, endothelial cells and hepatic stellate cells, the structure and physiological function of the liver Disse gap can be simulated, and the requirements of in-vitro liver physiological/pathological research, drug testing and drug development, tissue engineering and regenerative medicine are met. The artificial liver organ can be induced into various liver disease models at the same time, and corresponding pathological models can be constructed according to requirements.

Description

technical field [0001] The invention relates to the fields of biomaterials and biomedical engineering, in particular to an artificial liver organoid and its preparation method and application. Background technique [0002] The liver is the largest internal organ in the human body, and it undertakes physiological functions such as metabolism of toxic substances, metabolism and synthesis of lipids and carbohydrates. The space of disse in the liver is the physiological structure of the liver, which is composed of hepatic parenchymal cells, hepatic sinusoidal endothelial cells, hepatic stellate cells and extracellular matrix components. Hepatic parenchymal cells undertake multiple functions such as biosynthesis, lipid metabolism and detoxification. The microvessel structure formed by hepatic sinusoidal endothelial cells is the site for material exchange between hepatocytes and blood, and blood flow stimulation in microvessels plays an important role in the process of liver stru...

Claims

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Application Information

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IPC IPC(8): C12N5/071
CPCC12N5/067C12N2513/00C12N2533/74C12N2533/54C12N2533/40
Inventor 姚睿梁少君罗依雪陈若瑜申函宁薛胜楠
Owner TSINGHUA UNIV
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