脑类器官在再生医学中的研究进展

洪源; 刘妍

doi:10.12211/2096-8280.2023-102

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脑类器官在再生医学中的研究进展

特约评述 | 更新时间：2025-03-19

- 脑类器官在再生医学中的研究进展
- Research progress of brain organoids in regenerative medicine
- 合成生物学 2024年5卷第4期页码：754-769
- 作者机构：
  
  1.南京医科大学姑苏学院，江苏南京 211166
  2.苏州市立医院，江苏苏州 215006
  3.南京医科大学附属苏州医院，江苏苏州 215006
  4.南京医科大学生殖医学与子代健康全国重点实验室，江苏南京 211166
  5.南京医科大学药学院干细胞与神经再生研究所，江苏南京 211166
- 作者简介：
  
  [ "洪源（1995—），男，博士。研究方向为利用人脑类器官模型开展抑郁症病理机制研究。E-mail：justhongyuan@njmu.edu.cn" ]
  [ "刘妍（1981—），女，教授，博士生导师。研究方向为利用人脑类器官开展神经疾病机制及细胞移植治疗研究。E-mail：yanliu@njmu.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2021YFA1101800);国家自然科学基金(82171528);南京医科大学姑苏学院博士后科研项目(GSBSHKY202307)
- DOI：10.12211/2096-8280.2023-102
  中图分类号： Q81
- 收稿：2023-12-01，
  
  修回：2024-05-29，
  
  纸质出版：2024-08-31
- 稿件说明：
移动端阅览
洪源，刘妍. 脑类器官在再生医学中的研究进展［J］. 合成生物学， 2024， 5（4）： 754-769

HONG Yuan， LIU Yan. Research progress of brain organoids in regenerative medicine［J］. Synthetic Biology Journal， 2024， 5（4）： 754-769
洪源，刘妍. 脑类器官在再生医学中的研究进展［J］. 合成生物学， 2024， 5（4）： 754-769 DOI： 10.12211/2096-8280.2023-102.

HONG Yuan， LIU Yan. Research progress of brain organoids in regenerative medicine［J］. Synthetic Biology Journal， 2024， 5（4）： 754-769 DOI： 10.12211/2096-8280.2023-102.

摘要

脑类器官是一种基于人多能干细胞的三维体外模型，能够模拟人脑的细胞异质性、结构和功能。再生医学是一个多学科交叉的领域，致力于应用工程学和生物学手段修复因年龄、疾病或外伤而受损的组织或器官。脑类器官技术作为再生医学领域的一种重要手段，具有广阔的应用前景和重要的科学意义。近年来，利用组织工程和诱导因子分化技术，研究人员成功构建出不同脑区的脑类器官模型，可用于模拟脑损伤或修复病变组织。本文将系统介绍包括大脑皮层、海马、纹状体、中脑、丘脑及下丘脑、小脑和视网膜在内的脑区特异类器官构建技术的最新进展，总结其在再生医学领域中的应用，并概括当前脑类器官应用面临的挑战，如异质性大、缺乏脉管系统和成熟度较低等。这将加深对人类大脑的理解，并增强脑类器官在基础研究和临床研究中的进一步应用。

Abstract

The brain

as the epicenter of human intelligence

sensation

and motor coordination

represents the pinnacle of biological complexity. Despite its critical role

the availability of live human brain tissue for research is fraught with challenges

impeding advancements in our understanding of the nervous system. Brain organoids are sophisticated three-dimensional cultures derived from human pluripotent stem cells that emulate the diverse cellular composition

structural intricacies

and functional attributes of the human brain. These organoids eclipse traditional two-dimensional cultures and animal models in mirroring the brain’s spatial organization and cellular interplay

bolstered by a genetic congruence with their human counterparts. This congruence renders them particularly adept at modeling neuropsychiatric conditions and pioneering cell-based therapeutic interventions. Regenerative medicine

a confluence of engineering and biological sciences

endeavors to restore tissues and organs compromised by aging

disease

or trauma. However

the field grapples with limitations stemming from the scarcity of samples and ethical quandaries. Brain organoid technology emerges as a formidable asset in this domain

offering expansive potential and profound implications for scientific inquiry. Recent strides have seen the successful assembly of organoid models representing various brain regions through the application of tissue engineering and directed differentiation. These models hold promise for simulating neuropathological states and facilitating tissue repair. This article meticulously surveys the cutting-edge methodologies for constructing organoids specific to brain regions such as the cerebral cortex

hippocampus

striatum

midbrain

thalamus

hypothalamus

cerebellum

and retina. It delineates the principal applications of brain organoids in regenerative medicine

encompassing injury simulation

exploration of inter-regional and multi-lineage cellular dynamics

drug efficacy and toxicity assessments

and the potential for organoid transplantation. Furthermore

the review addresses the prevailing obstacles in the application of brain organoids

notably their pronounced variability

absence of vascularization

and developmental immaturity. In essence

this review seeks to illuminate the organoid generation techniques tailored to discrete brain territories and their significance in regenerative medicine’s landscape. By probing into research poised to surmount the limitations of current models

it aspires to broaden the horizons for brain organoids in both foundational research and clinical applications.

关键词

Keywords

references

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