脑类器官中提高成熟度和细胞复杂性的移植策略。
Transplantation Strategies to Enhance Maturity and Cellular Complexity in Brain Organoids.
机构信息
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California.
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California.
出版信息
Biol Psychiatry. 2023 Apr 1;93(7):616-621. doi: 10.1016/j.biopsych.2023.01.004. Epub 2023 Jan 13.
Abstract
Human brain organoids are 3-dimensional cell aggregates that are generated from pluripotent stem cells and recapitulate features of the early developing human brain. Brain organoids mainly consist of cells from the neural lineage, such as neural progenitor cells, neurons, and astrocytes. However, current brain organoid systems lack functional vasculature as well as other non-neuronal cells that are indispensable for oxygen and nutrient supply to the organoids, causing cell stress and formation of a necrotic center. Attempts to utilize intracerebral transplantation approaches have demonstrated successful vascularization of brain organoids and robust neurodifferentiation. In this review, we summarize recent progress and discuss ethical considerations in the field of brain organoid transplantation.
摘要
人脑类器官是由多能干细胞生成的 3 维细胞聚集体，可重现早期人类大脑的特征。人脑类器官主要由神经谱系细胞组成，如神经祖细胞、神经元和星形胶质细胞。然而，目前的人脑类器官系统缺乏功能性血管以及其他对类器官的氧和营养供应必不可少的非神经细胞，导致细胞应激和坏死中心形成。利用脑内移植方法的尝试已经证明了脑类器官的血管化和强大的神经分化。在这篇综述中，我们总结了该领域的最新进展，并讨论了脑类器官移植的伦理考虑。
相似文献
1
Transplantation Strategies to Enhance Maturity and Cellular Complexity in Brain Organoids.脑类器官中提高成熟度和细胞复杂性的移植策略。
Biol Psychiatry. 2023 Apr 1;93(7):616-621. doi: 10.1016/j.biopsych.2023.01.004. Epub 2023 Jan 13.
2
Vascularization of human brain organoids.人脑类器官的血管化。
Stem Cells. 2021 Aug;39(8):1017-1024. doi: 10.1002/stem.3368. Epub 2021 Mar 31.
3
Cellular complexity in brain organoids: Current progress and unsolved issues.脑类器官中的细胞复杂性：当前进展与未解决的问题。
Semin Cell Dev Biol. 2021 Mar;111:32-39. doi: 10.1016/j.semcdb.2020.05.013. Epub 2020 Jun 1.
4
Method to Generate Dorsal Forebrain Brain Organoids from Human Pluripotent Stem Cells.从人类多能干细胞生成背侧前脑类脑器官的方法。
Methods Mol Biol. 2023;2683:169-183. doi: 10.1007/978-1-0716-3287-1_13.
5
Bioengineering tissue morphogenesis and function in human neural organoids.在人类神经类器官中生物工程组织形态发生和功能。
Semin Cell Dev Biol. 2021 Mar;111:52-59. doi: 10.1016/j.semcdb.2020.05.025. Epub 2020 Jun 12.
6
Toward the next generation of vascularized human neural organoids.迈向新一代血管化人类神经类器官。
Med Res Rev. 2023 Jan;43(1):31-54. doi: 10.1002/med.21922. Epub 2022 Aug 22.
7
Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality.人源中脑组织类器官中内源性小胶质细胞的整合导致神经元成熟和功能增强。
Glia. 2022 Jul;70(7):1267-1288. doi: 10.1002/glia.24167. Epub 2022 Mar 9.
8
Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium.人多能干细胞衍生的神经细胞和脑类器官揭示 SARS-CoV-2 的嗜神经性主要存在于脉络丛上皮。
Cell Stem Cell. 2020 Dec 3;27(6):937-950.e9. doi: 10.1016/j.stem.2020.09.016. Epub 2020 Sep 21.
9
Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology.利用可控的小胶质细胞比例，开发基于人类多能干细胞的大脑类器官，用于模拟大脑发育和病理学。
Stem Cell Reports. 2021 Aug 10;16(8):1923-1937. doi: 10.1016/j.stemcr.2021.06.011. Epub 2021 Jul 22.
10
In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids.多能干细胞衍生脑类器官体外再现神经精神疾病。
Int J Environ Res Public Health. 2021 Nov 26;18(23):12431. doi: 10.3390/ijerph182312431.
引用本文的文献
1
Brain Organoid Transplantation: A Comprehensive Guide to the Latest Advances and Practical Applications-A Systematic Review.脑类器官移植：最新进展与实际应用的全面指南——一项系统综述
Cells. 2025 Jul 14;14(14):1074. doi: 10.3390/cells14141074.
2
Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine.神经类器官的生成及其在疾病建模和再生医学中的应用。
Adv Sci (Weinh). 2025 Aug;12(29):e01198. doi: 10.1002/advs.202501198. Epub 2025 May 24.
3
Expanding the neuroimmune research toolkit with in vivo brain organoid technologies.利用体内脑类器官技术扩展神经免疫研究工具集。
Dis Model Mech. 2025 Apr 1;18(4). doi: 10.1242/dmm.052200. Epub 2025 Apr 15.
4
Progress in spinal cord organoid research: advancing understanding of neural development, disease modelling, and regenerative medicine.脊髓类器官研究进展：加深对神经发育、疾病建模和再生医学的理解
Biomater Transl. 2024 Nov 15;5(4):355-371. doi: 10.12336/biomatertransl.2024.04.003. eCollection 2024.
5
The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.典型的干扰素病：从床边到实验室的 Aicardi-Goutières 综合征。
Immunol Rev. 2024 Oct;327(1):83-99. doi: 10.1111/imr.13413. Epub 2024 Oct 29.
6
Human-Mouse Chimeric Brain Models to Study Human Glial-Neuronal and Macroglial-Microglial Interactions.用于研究人类神经胶质细胞与神经元以及大胶质细胞与小胶质细胞相互作用的人鼠嵌合脑模型
bioRxiv. 2024 Dec 22:2024.07.03.601990. doi: 10.1101/2024.07.03.601990.
7
Brain organoid protocols and limitations.脑类器官培养方案及局限性。
Front Cell Neurosci. 2024 Mar 20;18:1351734. doi: 10.3389/fncel.2024.1351734. eCollection 2024.
8
Human brain organoid: trends, evolution, and remaining challenges.人类脑类器官：趋势、演变及尚存的挑战。
Neural Regen Res. 2024 Nov 1;19(11):2387-2399. doi: 10.4103/1673-5374.390972. Epub 2023 Dec 15.
9
Applications of multiphoton microscopy in imaging cerebral and retinal organoids.多光子显微镜在脑类器官和视网膜类器官成像中的应用。
Front Neurosci. 2024 Mar 5;18:1360482. doi: 10.3389/fnins.2024.1360482. eCollection 2024.
10
Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids.小行星撞击：星形胶质细胞调节类器官内人类神经网络的潜力。
Front Neurosci. 2023 Nov 22;17:1305921. doi: 10.3389/fnins.2023.1305921. eCollection 2023.
本文引用的文献
1
Maturation and circuit integration of transplanted human cortical organoids.移植的人类皮质类器官的成熟和回路整合。
Nature. 2022 Oct;610(7931):319-326. doi: 10.1038/s41586-022-05277-w. Epub 2022 Oct 12.
2
Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets.Gruffi：一种从脑类器官转录组数据集中计算去除应激细胞的算法。
EMBO J. 2022 Sep 1;41(17):e111118. doi: 10.15252/embj.2022111118. Epub 2022 Aug 2.
3
Generation of vascularized brain organoids to study neurovascular interactions.生成血管化的脑类器官以研究神经血管相互作用。
Elife. 2022 May 4;11:e76707. doi: 10.7554/eLife.76707.
4
Engineering neurovascular organoids with 3D printed microfluidic chips.利用3D打印微流控芯片构建神经血管类器官
Lab Chip. 2022 Apr 12;22(8):1615-1629. doi: 10.1039/d1lc00535a.
5
In vivo development and single-cell transcriptome profiling of human brain organoids.人类脑类器官的体内发育和单细胞转录组谱分析。
Cell Prolif. 2022 Mar;55(3):e13201. doi: 10.1111/cpr.13201. Epub 2022 Feb 10.
6
Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice.人脑类器官移植减轻了创伤性脑损伤小鼠的神经功能缺损。
Oxid Med Cell Longev. 2021 Nov 22;2021:6338722. doi: 10.1155/2021/6338722. eCollection 2021.
7
Human Blood Vessel Organoids Penetrate Human Cerebral Organoids and Form a Vessel-Like System.人血血管类器官可穿透人脑类器官并形成类似血管的系统。
Cells. 2021 Aug 9;10(8):2036. doi: 10.3390/cells10082036.
8
Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo.脑类器官：体外与体内研究人类神经生物学的接口
Nat Neurosci. 2020 Dec;23(12):1496-1508. doi: 10.1038/s41593-020-00730-3. Epub 2020 Nov 2.
9
Human cerebral organoids establish subcortical projections in the mouse brain after transplantation.人类大脑类器官在移植到小鼠大脑后建立皮质下投射。
Mol Psychiatry. 2021 Jul;26(7):2964-2976. doi: 10.1038/s41380-020-00910-4. Epub 2020 Oct 13.
10
Axonal Extensions along Corticospinal Tracts from Transplanted Human Cerebral Organoids.移植的人源大脑类器官中的皮质脊髓束中的轴突延伸。
Stem Cell Reports. 2020 Aug 11;15(2):467-481. doi: 10.1016/j.stemcr.2020.06.016. Epub 2020 Jul 16.
Zotero 插件