Marti-Figueroa Carlos R, Ashton Randolph S
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, United States.
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, United States.
Acta Biomater. 2017 May;54:35-44. doi: 10.1016/j.actbio.2017.03.023. Epub 2017 Mar 16.
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.
Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis to generate organoids with biomimicry at all scales. Such advancements would enable the use of organoids as a basis for 'next-generation' tissue engineering of functional, anatomically mimetic human tissues and potentially novel organ transplants. Here, we discuss critical aspects of organoid morphogenesis where application of innovative tissue engineering methodologies would yield significant advancement towards this goal.
源自人类多能干细胞（hPSC）衍生物的三维类器官已成为研究发育和疾病的广泛应用的体外模型。它们在体外形态发生过程中重现正常人类发育方面的能力产生了具有前所未有的生物模拟性的组织结构。当前的类器官衍生方案主要依赖于在三维球形细胞聚集体内发生的自发形态发生过程，几乎没有或没有外部控制。这产生了包含生物模拟组织微尺度区域的类器官，但在宏观尺度上（即数百微米到毫米），类器官的形态、细胞结构和细胞组成是非生物模拟的且可变的。目前在微尺度上对体外类器官形态发生缺乏控制会在宏观尺度上引发畸变，这阻碍了该技术可重复形成解剖学上正确的人类组织单元的潜力的实现，这些组织单元可作为最佳的人类体外模型甚至移植材料。在这里，我们综述了可用于开发强大方法来指导多尺度三维人类类器官形态发生的组织工程方法。这种技术融合对于将类器官形态发生作为一种工具来构建具有生物模拟解剖学和生理学的功能性人类组织至关重要。
源自人类多能干细胞的三维类器官正在彻底改变生物医学科学。它们能够在患者特异性遗传背景和前所未有的生物模拟组织微环境中研究发育和疾病。然而，它们在微尺度上不受控制的自发形态发生导致宏观尺度上类器官形态、细胞结构和细胞组成的不一致，这限制了它们的标准化和应用。将组织工程方法与类器官衍生方案相结合，可以通过指导标准化的体外形态发生来利用它们的潜力，以生成在所有尺度上都具有生物模拟性的类器官。这样的进展将使类器官能够作为功能性、解剖学模拟的人类组织的“下一代”组织工程以及潜在的新型器官移植的基础。在这里，我们讨论了类器官形态发生的关键方面，在这些方面应用创新的组织工程方法将朝着这一目标取得重大进展。
