A TISSUE-ENGINEERED PLACENTAL BARRIER MODEL FOR TOXICOLOGY AND PHARMACOLOGY APPLICATIONS

Abstract

Throughout history, there have been two major instances where a substance caused thousands of birth defects, yet it took a few years for the causation to be noted: thalidomide, in the late 1950s and early 1960s, and Zika Virus, just recently in 2014 to 2016. In both instances, the developing fetus was indirectly exposed to the substance through the placental barrier. Pregnant women took thalidomide as a medication or were stung by mosquitos and exposed to Zika Virus. These examples clearly show why models of the placental barrier and downstream fetal tissues are critically needed. Herein, I present our work on the development and utilization of a biomimetic placenta-fetus model. The three objectives in this work were to: (1) develop and validate the tissue-engineered BPB model through study of biologically relevant substances; (2) assess the effects of SSRIs on the BPB’s cells and evaluate the drugs’ transport profile across the barrier; and, (3) assess how SSRIs influence cardiomyocyte signaling and injury biomarker release following passage through the BPB. We suggest that this work provides a critically needed and biologically relevant placenta-fetus model, useful as a method to assess pharmacology and toxicology properties of medications and other substances. Moreover, the knowledge gained through the studies performed may hopefully improve clinical care of pregnant women through enhanced understanding of how a medication impacts both the pregnant mother-to-be and her developing fetus.