A Bioengineered Model for Studying Vascular-Pericyte Interactions of the Placenta

Investigating the complex cellular interactions of the placenta has remained, until now, a challenge in the field. Given the ethical limitations of studying human placentae, and the interspecies differences that exist between mammals, in vitro models are a valuable tool for investigating developmental and pathologic processes related to the human placenta. A number of in vitro models have been recently employed to investigate various aspects of placental development, with many focusing on the maternal-fetal interface including the trophoblasts and an endothelial barrier. One critical aspect in mimicking the physiology of the placenta is to include perfusable microvessels. As this organ is highly vascularized, it is pertinent to represent the exchange of oxygen and nutrients from the maternal blood to the embedded vessels of the fetus. Using hydrogel-laden microfluidics, it is now possible to bioengineer these and other microvessels in a reproducible manner. By using HUVEC, fetal-like vessels can be generated on a chip and can be studied in a controlled manner. This chapter introduces the concept of generating a triculture vasculature on-chip system, which can be employed to study placental pericyte-endothelial interactions. We describe strategies for generating the vessels on-chip, as well as for quantifying vascular morphology and function. This methodology allows for unique microvessel-related biological questions to be addressed, including how stromal cells impact vascular remodeling over time.