The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.
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DOI:
10.1016/j.actbio.2017.03.023
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发表时间:
2017-05
期刊:
影响因子:
9.7
通讯作者:
Ashton RS
Ashton RS
中科院分区:
工程技术1区
文献类型:
--
作者:
Marti-Figueroa CR;Ashton RS

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衍生自人多能干细胞(hPSC)衍生物的三维类器官已广泛用于研究发育和疾病的体外模型。它们能够在体外形态发生过程中重现正常人类发育的各个方面,从而产生具有前所未有的仿生学的组织结构。目前的类器官衍生方案主要依赖于自发的形态发生过程中发生的3-D球形细胞聚集体与最小或没有外源性控制。这产生含有仿生组织的微尺度区域的类器官,但在宏观尺度(即数百微米至毫米),类器官的形态、细胞结构和细胞组成是非仿生的和可变的。目前在微观尺度上缺乏对体外类器官形态发生的控制会导致宏观尺度上的畸变,这阻碍了该技术可再现地形成解剖学上正确的人体组织单位的潜力的实现,这些组织单位可以用作最佳的人体体外模型甚至移植物。在这里,我们回顾组织工程方法,可用于开发强大的方法,指导多尺度,三维人体类器官形态发生。迫切需要这种技术合并来利用类器官形态发生作为利用仿生解剖学和生理学工程功能性人体组织的工具。
Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100’s of microns to millimeters), the organoids’ morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology’s potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology.
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