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Application of humanized brain-like organ to brain injury dyskinesia disease

A movement disorder and brain injury technology, applied in the field of brain science, to achieve the effect of good balance beam exercise ability and improvement of neuromuscular function

Inactive Publication Date: 2018-11-23
SHANGHAI FENGJING BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The Chinese patent application 201810417891.9 with an application date of May 4, 2018 relates to the culture method of humanized brain organoids and their use in the construction of ischemia models. There is no research report on whether the transplantation in the disease can improve the movement disorder after brain injury, etc.

Method used

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  • Application of humanized brain-like organ to brain injury dyskinesia disease
  • Application of humanized brain-like organ to brain injury dyskinesia disease
  • Application of humanized brain-like organ to brain injury dyskinesia disease

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Example 1: Culture of Brain Organoids

[0036] According to references (Nature 2013; 501:373-379 and Nat Protoc 2014; 9:2329-2340), after a series of explorations and improvements, the ultra-low adsorption well plate and rotary biogenerator culture system were adopted successively, and human pluripotent stem cells After successively undergoing germ layer differentiation, neuroectoderm differentiation, and neuroepithelial tissue formation, humanized brain organoids with 3D structures have been induced in rotary flasks. The culture stages are as follows.

[0037] The first stage: In the ultra-low adsorption 96-well plate, according to the living cell density 9×10 4 cells / mL, inoculated 150 μL per well to obtain embryonic small body-like cell clusters ( figure 1 , 2 days shown).

[0038] The second stage: continue to induce differentiation, the embryonic body begins to show the characteristics of germ layer differentiation, and induces the initial neuroepithelial tissue ...

Embodiment 2

[0041] Example 2: Brain organoids used in brain injury transplantation

[0042] experimental method

[0043] 1. Construction of rat brain trauma model and brain transplantation

[0044] Adult SD rats, weighing about 300 g, were purchased from Shanghai Slack Experimental Animal Co., Ltd. The day before the operation, cyclosporine A (LC Labs C6000) 10 mg / kg was administered intraperitoneally. Rats were anesthetized by intraperitoneal injection, and then the head hair was shaved with a shaver, and fixed on a mouse brain stereotaxic apparatus. Wipe the rat scalp with 75% alcohol for disinfection, make a longitudinal incision about 4 cm long along the midline of the brain with a scalpel, separate the surface fascia of the skull, and fully expose the skull. In the right hemibrain of the rat, a rectangular skull window with a length of 1.5 cm and a width of 0.6 cm was drilled with a skull drill to expose the cortex of the rat. The mouse brain stereotaxic instrument was used as th...

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Abstract

The invention relates to a novel use of a humanized brain-like organ, i.e., application of the humanized brain-like organ to preparation of a transplant for treating brain injury. The application hasthe advantages that compared with a traumatic brain injury group, brain-like transplantation can promote regeneration of nerves of a traumatic brain injury sport cortical area and a lateral ventriclearea; 7, 14 and 28 days after transplantation, existence of brain-like tissue cells can be detected in the traumatic brain injury sport cortical area, and the feasibility of survival after the brain-like transplantation is proved. Results of nerve muscle function tests and balance beam tests show that, compared with the traumatic brain injury group, 7 days after an operation, brain-like transplantation can obviously improve the nerve muscle function and has better balance beam athletic ability.

Description

technical field [0001] The invention relates to the technical field of brain science, in particular to the application of humanized brain organoids in brain injury movement disorders. Background technique [0002] Brain injury has a high morbidity and mortality rate, but lacks effective treatment and is a very serious social and health problem. Human induced pluripotent stem cells (iPSCs) can differentiate into almost all types of cells in vivo or in vitro, which can be used to simulate human development and disease occurrence, drug screening, cell replacement therapy, etc. A large number of preclinical studies have shown that stem cell transplantation treatment can promote the recovery of brain injury. However, traditional monolayer cell culture can only control the targeted differentiation of iPSCs into specific cell types, and cannot simulate the tissue assembly characteristics of three-dimensional (3D) cells in biological systems, and cannot achieve true functional repl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/38A61L27/50
CPCA61L27/3834A61L27/3878A61L27/3895A61L27/50A61L2430/32
Inventor 缪朝玉王淑娜王治徐添颖
Owner SHANGHAI FENGJING BIOMEDICAL TECH CO LTD
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