脑类器官技术及在脑卒中治疗中的应用进展

doi:10.11958/20231381

天津医药 ›› 2024, Vol. 52 ›› Issue (1): 38-43.doi: 10.11958/20231381

• 专题研究·类器官与器官芯片（主编·陈怀永） • 上一篇下一篇

脑类器官技术及在脑卒中治疗中的应用进展

孙可心¹(), 肖雨倩¹, 万俊¹, 陈淑颖¹, 陈丽敏¹, 王岩², 白艳杰²^,^△()

1.河南中医药大学（邮编450000）
2.河南中医药大学第一附属医院

收稿日期:2023-10-16 出版日期:2024-01-15 发布日期:2024-01-18
通讯作者: ^△E-mail：baiyj66@126.com
作者简介:孙可心（2000），女，硕士在读，主要从事脑卒中后认知障碍研究。E-mail：565049543@qq.com
基金资助:
河南省中医药科学研究专项重点课题(20-21ZY1009);河南省中医药传承与创新人才工程（仲景工程）中医药学科拔尖人才(CZ0237-08);河南省科技攻关计划(222102310529);河南省卫健委国家中医临床研究基地科研专项(2022JDZX005);河南省中医药拔尖人才培养项目专项课题(2022ZYBJ07)

Research progress of cerebral organoid technology and its application in stroke treatment

SUN Kexin¹(), XIAO Yuqian¹, WAN Jun¹, CHEN Shuying¹, CHEN Limin¹, WANG Yan², BAI Yanjie²^,^△()

1. Henan University of Chinese Medicine, Zhengzhou 450000, China
2. the First Affiliated Hospital of Henan University of Chinese Medicine

Received:2023-10-16 Published:2024-01-15 Online:2024-01-18
Contact: ^△E-mail：baiyj66@126.com

孙可心, 肖雨倩, 万俊, 陈淑颖, 陈丽敏, 王岩, 白艳杰. 脑类器官技术及在脑卒中治疗中的应用进展[J]. 天津医药, 2024, 52(1): 38-43.

SUN Kexin, XIAO Yuqian, WAN Jun, CHEN Shuying, CHEN Limin, WANG Yan, BAI Yanjie. Research progress of cerebral organoid technology and its application in stroke treatment[J]. Tianjin Medical Journal, 2024, 52(1): 38-43.

摘要/Abstract

摘要：

脑类器官是一种由胚胎干细胞（ESCs）或诱导多能干细胞（iPSCs）诱导产生的三维神经培养物，能够模拟人脑的结构和功能。随着脑类器官培养技术的不断优化，并与器官移植、基因编辑和类器官芯片等新兴技术相结合，产生了功能性血管结构和神经回路等复杂脑组织结构，为研究人类大脑发育和疾病提供了新方法、新思路。就脑类器官技术的最新进展进行综述，阐述了其在神经系统疾病中的应用，以及在脑卒中建模和移植治疗中的进展。

关键词: 类器官, 移植, 芯片分析技术, 卒中, 脑类器官

Abstract:

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) that mimic the structure and function of human brain. With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation, gene editing and organoids-on-chip, complex brain tissue structures such as functional vascular structures and neural circuits have been produced, which provides new methods and ideas for studying human brain development and diseases. This article reviews the latest advances in brain organoid technology, describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Key words: organoids, transplantation, microchip analytical procedures, stroke, cerebral organoid

中图分类号:

R318，R743.3

图/表 1

参考文献 38

[1]	FEIGIN V L, STARK B A, JOHNSON C O, et al. Global,regional,and national burden of stroke and its risk factors,1990-2019:A systematic analysis for the global burden of disease study 2019[J]. Lancet Neurol, 2021, 20(10):795-820. doi:10.1016/s1474-4422(21)00252-0.
[2]	CAMPBELL B C V, KHATRI P. Stroke[J]. Lancet, 2020, 396(10244):129-142. doi:10.1016/S0140-6736(20)31179-X.
[3]	LANCASTER M A, RENNER M, MARTIN C A, et al. Cerebral organoids model human brain development and microcephaly[J]. Nature, 2013, 501(7467):373-379. doi:10.1038/nature12517.
[4]	SIDHAYE J, KNOBLICH J A. Brain organoids:An ensemble of bioassays to investigate human neurodevelopment and disease[J]. Cell Death Differ, 2021, 28(1):52-67. doi:10.1038/s41418-020-0566-4.
[5]	REVAH O, GORE F, KELLEY K W, et al. Maturation and circuit integration of transplanted human cortical organoids[J]. Nature, 2022, 610(7931):319-326. doi:10.1038/s41586-022-05277-w.
[6]	SUN N, MENG X Q, LIU Y X, et al. Applications of brain organoids in neurodevelopment and neurological diseases[J]. J Biomed Sci, 2021, 28(1):30. doi:10.1186/s12929-021-00728-4.
[7]	LANCASTER M A, CORSINI N S, WOLFINGER S, et al. Guided self-organization and cortical plate formation in human brain organoids[J]. Nat Biotechnol, 2017, 35(7):659-666. doi:10.1038/nbt.3906.
[8]	GIANDOMENICO S L, MIERAU S B, GIBBONS G M, et al. Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output[J]. Nat Neurosci, 2019, 22(4):669-679. doi:10.1038/s41593-019-0350-2.
[9]	CAKIR B, XIANG Y F, TANAKA Y, et al. Engineering of human brain organoids with a functional vascular-like system[J]. Nat Methods, 2019, 16(11):1169-1175. doi:10.1038/s41592-019-0586-5.
[10]	QIAN X Y, SONG H J, MING G L. Brain organoids:Advances,applications and challenges[J]. Development, 2019, 146(8):dev166074. doi:10.1242/dev.166074.
[11]	JACOB F, PATHER S R, HUANG W K, et al. Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-Cov-2 neurotropism predominates in choroid plexus epithelium[J]. Cell Stem Cell, 2020, 27(6):937-950. doi:10.1016/j.stem.2020.09.016.
[12]	HUANG W K, WONG S Z H, PATHER S R, et al. Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells[J]. Cell Stem Cell, 2021, 28(9):1657-1670. doi:10.1016/j.stem.2021.04.006.
[13]	TANG X Y, WU S S, WANG D, et al. Human organoids in basic research and clinical applications[J]. Signal Transduct Target Ther, 2022, 7(1):168. doi:10.1038/s41392-022-01024-9.
[14]	JEONG E, CHOI S, CHO S W. Recent advances in brain organoid technology for human brain research[J]. ACS Appl Mater Interfaces, 2023, 15(1):200-219. doi:10.1021/acsami.2c17467.
[15]	CHEN H, JIN X, LI T, et al. Brain organoids:Establishment and application[J]. Front Cell Dev Biol, 2022, 10:1029873. doi:10.3389/fcell.2022.1029873.
[16]	HUANG S C, HUANG F, ZHANG H Y, et al. In vivo development and single-cell transcriptome profiling of human brain organoids[J]. Cell Prolif, 2022, 55(3):e13201. doi:10.1111/cpr.13201.
[17]	WANG Z, WANG S N, XU T Y, et al. Cerebral organoids transplantation improves neurological motor function in rat brain injury[J]. CNS Neurosci Ther, 2020, 26(7):682-697. doi:10.1111/cns.13286.
[18]	ZHENG X, HAN D Q, LIU W H, et al. Human IPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease[J]. Theranostics, 2023, 13(8):2673-2692. doi:10.7150/thno.80271.
[19]	KURISHEV A O, KARPOV D S, NADOLINSKAIA N I, et al. CRISPR/CAS-based approaches to study schizophrenia and other neurodevelopmental disorders[J]. Int J Mol Sci, 2023, 24(1):241. doi:10.3390/ijms24010241.
[20]	TANG X Y, XU L, WANG J S, et al. DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in ipsc-derived cerebral organoids from patients with down syndrome[J]. J Clin Invest, 2021, 131(12):e135763. doi:10.1172/jci135763.
[21]	ESK C, LINDENHOFER D, HAENDELER S, et al. A human tissue screen identifies a regulator of ER secretion as a brain-size determinant[J]. Science, 2020, 370(6519):935-941. doi:10.1126/science.abb5390.
[22]	FAIR S R, SCHWIND W, JULIAN D, et al. Cerebral organoids containing an AUTS2 missense variant model microcephaly[J]. Brain, 2023, 146(1):387-404. doi:10.1093/brain/awac244.
[23]	HE Z, MAYNARD A, JAIN A, et al. Lineage recording in human cerebral organoids[J]. Nat Methods, 2022, 19(1):90-99. doi:10.1038/s41592-021-01344-8.
[24]	CASTIGLIONE H, VIGNERON P-A, BAQUERRE C, et al. Human brain organoids-on-chip:Advances,challenges,and perspectives for preclinical applications[J]. Pharmaceutics, 2022, 14(11):2301. doi:10.3390/pharmaceutics14112301.
[25]	AKCAY G, LUTTGE R. Microenvironments matter:Advances in brain-on-chip[J]. Biosensors (Basel), 2023, 13(5):551. doi:10.3390/bios13050551.
[26]	WANG Y, WANG L, ZHU Y, et al. Human brain organoid-on-a-chip to model prenatal nicotine exposure[J]. Lab Chip, 2018, 18(6):851-860. doi:10.1039/c7lc01084b.
[27]	SALMON I, GREBENYUK S, FATTAH A R A, et al. Engineering neurovascular organoids with 3D printed microfluidic chips[J]. Lab Chip, 2022, 22(8):1615-1629. doi:10.1039/d1lc00535a.
[28]	CUI K, CHEN W, CAO R, et al. Brain organoid-on-chip system to study the effects of breast cancer derived exosomes on the neurodevelopment of brain[J]. Cell Regen, 2022, 11(1):7. doi:10.1186/s13619-021-00102-7.
[29]	KIM M S, KIM D-H, KANG H K, et al. Modeling of hypoxic brain injury through 3d human neural organoids[J]. Cells, 2021, 10(2):234. doi:10.3390/cells10020234.
[30]	WANG S N, WANG Z, WANG X Y, et al. Humanized cerebral organoids-based ischemic stroke model for discovering of potential anti-stroke agents[J]. Acta Pharmacol Sin, 2023, 44(3):513-523. doi:10.1038/s41401-022-00986-4.
[31]	IWASA N, MATSUI T K, IGUCHI N, et al. Gene expression profiles of human cerebral organoids identify ppar pathway and pkm2 as key markers for oxygen-glucose deprivation and reoxygenation[J]. Front Cell Neurosci, 2021, 15:605030. doi:10.3389/fncel.2021.605030.
[32]	WEVERS N R, NAIR A L, FOWKE T M, et al. Modeling ischemic stroke in a triculture neurovascular unit on-a-chip[J]. Fluids Barriers CNS, 2021, 18(1):59. doi:10.1186/s12987-021-00294-9.
[33]	PAWLUK H, WOZNIAK A, GRZESK G, et al. The role of selected pro-inflammatory cytokines in pathogenesis of ischemic stroke[J]. Clin Interv Aging, 2020, 15:469-484. doi:10.2147/cia.S233909.
[34]	SARMAH D, KAUR H, SARAF J, et al. Getting closer to an effective intervention of ischemic stroke:The big promise of stem cell[J]. Transl Stroke Res, 2018, 9(4):356-374. doi:10.1007/s12975-017-0580-0.
[35]	KITAHARA T, SAKAGUCHI H, MORIZANE A, et al. Axonal extensions along corticospinal tracts from transplanted human cerebral organoids[J]. Stem Cell Reports, 2020, 15(2):467-481. doi:10.1016/j.stemcr.2020.06.016.
[36]	CAO S Y, YANG D, HUANG Z Q, et al. Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke[J]. NPJ Regen Med, 2023, 8(1):27. doi:10.1038/s41536-023-00301-7.
[37]	WANG S N, WANG Z, XU T Y, et al. Cerebral organoids repair ischemic stroke brain injury[J]. Transl Stroke Res, 2020, 11(5):983-1000. doi:10.1007/s12975-019-00773-0.
[38]	CAO S Y, TAO M D, LOU S N, et al. Functional reconstruction of the impaired cortex and motor function by hmgeos transplantation in stroke[J]. Biochem Biophys Res Commun, 2023, 671:87-95. doi:10.1016/j.bbrc.2023.06.010.

脑类器官技术及在脑卒中治疗中的应用进展

Research progress of cerebral organoid technology and its application in stroke treatment

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