中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (5): 1013-1019.doi: 10.4103/1673-5374.385280

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊髓类器官研究应用的现在与未来

  

  • 出版日期:2024-05-15 发布日期:2023-10-31
  • 基金资助:
    国家重点研发计划(2018YFA0108602),中国医学科学院医学创新工程基金(CIFMS, 2021-I2M-C&T-B-016),中央高水平医院临床科研项目基金(2022-PUMCH-B-112)

Progress in the generation of spinal cord organoids over the past decade and future perspectives

Gang Zhou1, Siyuan Pang1, Yongning Li1, 2, Jun Gao1, *   

  1. 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; 2Department of International Medical Service, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Jun Gao, MD, PhD, gaojpumch@hotmail.com.
  • Supported by:
    This work was supported by the sup-project of National Key R&D Program of China, No. 2018YFA0108602; CAMS Innovation Fund for Medical Sciences, No. CIFMS, 2021-I2M-C&T-B-016; and National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-B-112 (all to JG).

摘要:

脊髓类器官是来源于干细胞的三维组织,可模拟体内脊髓的主要形态和功能特征。由于新兴的生物工程方法不断优化培养方案,综述通过回顾过去10年脊髓类器官在培养技术、表型以及在具体疾病中的应用,发现目前的脊髓类器官不仅可动态模拟神经管的形成,而且可沿着背腹侧和头侧尾轴表现出细胞结构的多样性。此外,融合运动神经元和其他区域特异性类器官的融合类脊髓器官可表现出复杂的神经回路,并可对类脊髓器官进行功能评估。这些特性使脊髓类器官成为疾病建模、药物筛选和组织再生的宝贵工具。通过对类脊髓器官的研究,研究者已在脊髓疾病的发病机制和潜在的治疗靶点方面取得了重大进展。然而,目前的脊髓类器官技术仍处于起步阶段,尚未得到广泛的转化应用。下一代脊髓类器官的构建依赖于生产质量管理规范的出台,以及更加关注生物电刺激和电生理功能评估等。

https://orcid.org/0000-0003-1520-0235 (Jun Gao)

关键词: 脊髓类器官, 多能干细胞, 类器官芯片, 融合类器官, 神经发育疾病, 神经退行性疾病, 脊髓损伤

Abstract: Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo. As emerging bioengineering methods have led to the optimization of cell culture protocols, spinal cord organoids technology has made remarkable advancements in the past decade. Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes. Moreover, fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment. These qualities make spinal cord organoids valuable tools for disease modeling, drug screening, and tissue regeneration. By utilizing this emergent technology, researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases. However, at present, spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine. Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation. 

Key words: development, organoid-on-a-chip, pluripotent stem cells, progress, spinal cord diseases, spinal cord organoids, vascularization