源自人多能干细胞(hPSC)衍生物的三维类器官已经广泛用于体外模型中,用于研究发育和疾病。它们在体外形态发生过程中概括正常人类发育方面的能力产生了具有前所未有的仿生能力的组织结构。当前的类器官衍生方案主要依赖于在3-D球形细胞聚集体中发生的自发形态发生过程,而很少或没有外源控制。这产生了含有仿生组织的微尺度区域的类器官,但在宏观尺度(即100微米到毫米),类器官形态,细胞结构,和细胞组成是非仿生和可变的。目前在微观尺度上缺乏对体外类器官形态发生的控制,这阻碍了实现该技术的潜力,可重复地形成解剖学上正确的人体组织单位,可以作为最佳的人体体外模型,甚至移植。这里,我们回顾了组织工程方法,这些方法可用于开发强大的方法来指导多尺度,3-D人类类器官形态发生。迫切需要这种技术合并,以利用类器官形态发生作为具有仿生解剖学和生理学的功能性人体组织工程的工具。
人类PSC衍生的3-D类器官正在彻底改变生物医学科学。它们能够在患者特定的遗传背景和前所未有的仿生组织微环境中研究发育和疾病。然而,他们不受控制,微尺度的自发形态发生产生了宏观类器官形态的不一致,细胞结构,和细胞组成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,可以使我们通过指导标准化的体外形态发生来利用其潜力,从而在所有规模上产生具有仿生能力的类器官。这样的进步将使得能够使用类器官作为“下一代”功能性组织工程的基础,解剖学模拟人体组织和潜在的新型器官移植。这里,我们讨论了类器官形态发生的关键方面,其中创新的组织工程方法的应用将在实现这一目标方面取得重大进展。
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.