Development of a placenta in a dish experimental system

Program Type (Grant): Innovation Grant
Applicant Name: Riddell, Meghan
Competition Cycle: 2019-03
Start Date: 2019-08-01
End Date: 2023-07-31
Institutional Sponsor: Medicine & Dentistry-Obstetrics & Gynecology
WCHRI Funder: RAHF/SCHF
Total WCHRI Funding Commitment: $48,508.00

The placenta is a critical organ regulating the growth and health of the developing fetus. This organ is responsible for the delivery of nutrients and oxygen to the fetus, removal of waste, and protection from infections. The development and proper function of the cells on the outermost surface of the placenta is particularly important since this is the site where all of these functions occur. Since the surface of the placenta is bathed in the mother's blood, it is a barrier between the mother and the fetus that must be overcome and is also a target of any drugs given to to the mother. Therefore, knowing how drugs effect these cells is important in predicting whether drugs meant to treat the pregnant mother or the fetus may have unintended side-effects in the placenta. The growth of organs in a dish has proven to be a powerful tool to enable research testing new drugs before they are introduced to people. This model is also useful for scientists to learn fundamentally imporant information about how cells function. Traditional methods of cell culture where a single layer of cells are attached to a plastic dish cannot properly mimic characteristics of tissues that are normally arranged in a three-dimensional manner. In particular, when we culture the cells that make up the outermost layers of the placenta they fail to grow and cannot carry out other functions they have when they are in the body. Very recently, methods have been developed for the growth of 'placentas in a dish' or placental organoids. Though a large step forward towards better models of the placenta than traditional methods, these new models form inside-out and therefore are not suitable for studies looking at things delivered to the placenta from the mother's blood. This includes studies about placental infection and drug delivery. In this project we will work to improve these new placentas in a dish to optimize them so that they form with the proper orientation. This will then allow for future studies looking at delivery of drugs and how infectious agents, such as paratises and viruses, infect the placenta and to understand how the placenta forms.