研究动态
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面向下一代血管化人类神经器官体。

Toward the next generation of vascularized human neural organoids.

发表日期:2023 Jan
作者: Minghui Li, Lixiong Gao, Ling Zhao, Ting Zou, Haiwei Xu
来源: MEDICINAL RESEARCH REVIEWS

摘要:

由于三维培养技术的进步,人类中枢神经系统的发育和疾病通过来源于人类胚胎干细胞(hESCs)或人类诱导多能干细胞(hiPSCs)的类器官组织得到逐步揭示,称为有机器官。自组织神经器官(NO)已被用于体外模拟特定器官的形态发生和功能。许多NO已经在体外重复出现,例如,模拟人类大脑、视网膜和脊髓的器官。然而,NO无法重现体内神经组织的成熟和复杂性。当前NO培养协议的持续问题是由于缺乏血管网络而导致氧气供应和营养扩散不足。在体内,发育的中枢神经系统被血管网络所穿透,血管不仅供应氧气和营养,还为神经生长提供结构模板。为了解决这些问题,最近的研究开始将NO培养与生物工程技术和方法相结合,包括遗传工程、共培养、多向分化、微流控技术、三维生物打印和移植等,这可能促进NO成熟并创建更加功能性的NO。这些尖端方法可以在体外生成更加可靠的NO模型,以破译人类中枢神经系统的发育、疾病进展和转化应用的密码。在本综述中,我们将总结最近文化策略的技术进展,生成带有血管的NO(vNOs),重点关注脑和视网膜器官模型。©2022 Wiley Periodicals LLC.
Thanks to progress in the development of three-dimensional (3D) culture technologies, human central nervous system (CNS) development and diseases have been gradually deciphered by using organoids derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). Selforganized neural organoids (NOs) have been used to mimic morphogenesis and functions of specific organs in vitro. Many NOs have been reproduced in vitro, such as those mimicking the human brain, retina, and spinal cord. However, NOs fail to capitulate to the maturation and complexity of in vivo neural tissues. The persistent issues with current NO cultivation protocols are inadequate oxygen supply and nutrient diffusion due to the absence of vascular networks. In vivo, the developing CNS is interpenetrated by vasculature that not only supplies oxygen and nutrients but also provides a structural template for neuronal growth. To address these deficiencies, recent studies have begun to couple NO culture with bioengineering techniques and methodologies, including genetic engineering, coculture, multidifferentiation, microfluidics and 3D bioprinting, and transplantation, which might promote NO maturation and create more functional NOs. These cutting-edge methods could generate an ever more reliable NO model in vitro for deciphering the codes of human CNS development, disease progression, and translational application. In this review, we will summarize recent technological advances in culture strategies to generate vascularized NOs (vNOs), with a special focus on cerebral- and retinal-organoid models.© 2022 Wiley Periodicals LLC.