Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature.

Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature.
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芯片上的血管化类器官:构建具有功能性血管系统的类器官的策略

DOI:
10.1039/d0lc01186j
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发表时间:
2021-02-09
期刊:
影响因子:
6.1
通讯作者:
Kamm RD
Kamm RD
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhang S;Wan Z;Kamm RD

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人类类器官自组织并从同质多能干细胞(PSC)分化而来,复制了其体内对应物的关键结构和功能特征。尽管类器官技术的快速发展及其多种应用,但实现真正体内样功能的主要限制是缺乏成熟的结构组织和对组织尺寸的限制,这两者都是缺乏功能性脉管系统的直接后果。在缺乏可灌注血管的情况下,类器官内的核心区域在发育过程中由于增加的代谢需求而迅速坏死,而仅通过扩散无法满足代谢需求。因此,在类器官模型中纳入功能性脉管系统对于它们超过几百微米的生长和超过胚胎和胎儿阶段的成熟是必不可少的。在这里,我们回顾了血管化类器官和体外毛细血管床工程的最新进展,并进一步探索将它们整合到基于微流体的平台上的策略,旨在体外建立整个类器官的灌注脉管系统。
Human organoids, self-organized and differentiated from homogenous pluripotent stem cells (PSC), replicate the key structural and functional characteristics of their in vivo counterparts. Despite the rapid advancement of organoid technology and its diverse applications, major limitations in achieving truly in vivo like functionality have been the lack of matured structural organization and constraints on tissue size, both of which are direct consequences of lacking a functional vasculature. In the absence of perfusable vessels, a core region within organoids quickly becomes necrotic during development due to increased metabolic demands that cannot be met by diffusion alone. Thus, incorporating functional vasculature in organoid models is indispensable for their growth in excess of several hundred microns and maturaturation beyond embryonic and fetal phase. Here, we review recent advancements in vascularizing organoids and engineering in vitro capillary beds, and further explore strategies to integrate them on a microfluidic based platform, aiming for establishing perfused vasculature throughout organoids in vitro.
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