Affiliation:
1. Department of Chemical Engineering McMaster University Hamilton ON L8S 4L8 Canada
2. School of Biomedical Engineering McMaster University Hamilton ON L8S 4L8 Canada
3. Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON L8S 4L8 Canada
4. Department of Pediatrics and the Graduate Programme in Medical Sciences McMaster University Hamilton ON L8S 4L8 Canada
Abstract
AbstractThe early‐stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later‐stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, predictive models of early‐ and late‐stage placental transport are created using blastocyst‐derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation results in a thinner, fused trophoblast layer, as well as an increase in human chorionic gonadotropin secretion, barrier permeability, and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirms this shift toward a differentiated trophoblast subtype. Vascularization results in a molecule type‐ and size‐dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects on placental barrier permeability and that this model can be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy.
Funder
Natural Sciences and Engineering Research Council of Canada
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials