Engineering the Organizer

项目总结： 再生和发展在亚毫米尺度上运行，使用进化的设计原则来 推动替代器官和新器官的自我组装。我们这个项目的目标是遵循以下原则 “组织者”，通过显微手术将一小群细胞移植到幼小的宿主组织中，以形成模式并 从幼嫩的组织中诱导器官原基。为了实现这一点，我们首先确定了生产稳定的方法 层状幼稚组织(即稳定的宿主组织)，并开发新的工具来组装这些层状组织 薄片(即，代替手动显微外科移植物)，以能够形成平面极化3D结构。这个 推动现代组织工程的原理是基于形态发生的经典胚胎学研究 在有机化合物中。这些经典研究依赖于两栖动物模型，在这些模型中可以分离出特定的细胞 胚胎形成聚集体，并分化成独特的组织。以下是排序和排序程序 在吞噬和分化过程中，细胞自组装成具有不同极性的平面极化片层。 从前到后，形成由多种细胞类型组成的组织，细胞密度高。现在，它被广泛地 认识到在胚胎发育过程中，类似的、保守的自组装程序塑造了人体组织， 再生和癌症进展。然而，目前设计复杂3D结构的努力受到 不能在高密度下复制和可靠地产生多种细胞类型的有组织的多层状组织 细胞密度。到目前为止，还没有一种组织工程方法能够重建多层极化的3D 类似于胚胎最早阶段形成的结构。将我们的经验用于 和胚胎组装组织方面的专业知识，我们利用组织者的原则，并设计稳定 具有平面极性的多层组织。基于我们已发表的3D胚胎组织成形方法 我们将暴露稳定这些薄层的细胞，并开发组装方法 来生产平面极化组织。快速转化为人类生物医学研究和组织 通过利用两栖动物胚胎模型的速度和可获得性来测试和翻译关键字 发现人类胚胎干细胞模型的组织者。我们设想，这一长期结果将是 该项目将改变设计和制造可以从人类细胞类型中获得的组织的努力 以及用于广泛的临床和研究应用的IPSCs。

Project Summary: Regeneration and development operate on the sub-millimeter scale, using evolved design principles to drive self-assembly of replacement and new organs. Our goal with this project is to follow the principle of 'the organizer', where a small group of cells are microsurgically grafted into a naive host tissues to pattern and induce organ primordia from the naive tissue. To achieve this we first identify methods to produce stable laminar sheets of naive tissue (i.e. stable host tissues), and to develop novel tools to assemble these laminar sheets, (i.e. in place of manual microsurgical grafts) to enable formation of planar polarized 3D structures. The principles that propel modern tissue engineering are based on classic embryological studies of morphogenesis in organoids. These classic studies relied on amphibian models where specified cells could be isolated from embryos, formed into aggregates, and differentiated into distinctive tissues. Following programs of sorting and engulfment, and differentiation, cells self-assemble planar, polarized laminar sheets with distinct polarity, e.g. anterior-to-posterior, to form tissues consisting of multiple cell types at high cell density. It is now widely recognized that similar, conserved programs of self-assembly shape human tissues during embryogenesis, regeneration, and cancer progression. However, current efforts to engineer complex 3D structures suffer from an inability to reproducibly and reliably generate organized multi-laminar tissues of multiple cell types at high cell density. To date, no tissue engineering approach is capable of recreating multi-laminar polarized 3D structures analogous to those that form at even the earliest stages in the embryo. Using our experience with and expertise in embryonically assembled tissues, we leverage principles of the organizer, and engineer stable multi-laminar tissues with planar polarity. Based on our published methods for shaping 3D embryonic tissues into laminar sheets, we will to expose the cellular that stabilize those sheets and to develop assembly methods to produce planar polarized tissues. Rapid translation to human biomedical research and tissue are made possible by leveraging the speed and accessibility of the amphibian embryonic model to test and translate key findings to human embryonic stem cell models of the organizer. We envision that the long term outcome of this project will transform efforts to engineer and manufacture tissues that can be sourced from human cell types and iPSCs for a wide range of clinical and research applications.