DEVELOPMENT OF A HUMAN PLACENTA VILLOUS MICROPERFUSION

体内接触人类胎盘的限制和 人类胎儿循环导致了一些疾病的发展 实验模型，虽然对某些方面非常有用 研究发现，不能充分体现胎盘在体内的功能。这些 模型可以分为两种类型。第一个是那些，例如主要的 培养的滋养层细胞，使精确的实验规范成为可能 条件允许详细观察，但缺乏结构关系 以及体内组织的表型表达。第二种是那些 保留结构拓扑并在中反映环境的影响 子宫、胎盘等体外小叶灌流，但其中不允许 在细胞水平上的操纵或观察。随着更多信息的发布 关于胎盘的分子和细胞功能，它是 找到一种方法，使诸如 在组织模型中可以检查胎盘离子或水的转运 确定它们如何在这个更复杂、多组件的系统中运行。它是 因此，有必要整合这两种模式，并开发一种新的方法 其中详细的细胞功能可以在初级组织中观察到。目标是 这个项目的目的是开发一种新的型号，绒毛膜 微灌注，这将使这些研究成为可能。在这个模型中，一个小的 绒毛膜树的碎片将被插管并通过 胎儿循环，同时对碎片进行超融合， 模拟母体循环。这将在...舞台上进行 一种荧光显微镜，能够观察到 合体细胞层或胎儿血管系统中，通过设计方法来保持， 插管并灌流绒毛碎片。第二个目标是验证 生化稳定性和组织结构测定的绒毛血流灌注 正直。这一模式将为新的调查提供基础。 胎盘运输、新陈代谢、信号和结构生物学。

The restrictions on in vivo access to the human placenta and the human fetal circulation have resulted in the development of a number of experimental models, which, while extremely useful for some aspects of investigation, fail to represent placental function in vivo adequately. These models can be divided into two types. The first are those, such as the primary cultured trophoblast, which enable specification of precise experimental conditions and allow detailed observation but lack the structural relationships and phenotypic expression of the tissue in vivo. The second are those which retain the structural topology and reflect the effects of the environment in utero, such as the placental in vitro lobule perfusion, but which do not permit manipulation or observation at the cellular level. As more information is obtained concerning molecular and cellular function of the placenta, it is becoming increasingly important to find a way in which processes such as transplacental ion or water transport can be examined in a tissue model to determine how they operate in this more complex, multi-component system. It is necessary therefore to integrate the two model types and develop a new approach in which detailed cellular function can be observed in primary tissue. The goal of this project is to develop a new model, the chorionic villous microperfusion, which will enable these investigations. In this model a small fragment of the chorionic villous tree will be cannulated and perfused through the fetal circulation, while the fragment is simultaneously superfused, simulating the maternal circulation. This will be carried out on the stage of an epifluoresence microscope, enabling observation of fluorescent probes in the syncytial layer or in the fetal vasculature, by devising methods to hold, cannulate and perfuse villous fragments. The second aim is to validate the villous perfusion through measurements of biochemical stability and structural integrity. This model will provide the basis for new investigations in placental transport, metabolism, and signaling and structural biology.