Development of an Organ-on-a-Chip-Device for Study of Placental Pathologies.

Babak Mosavati,E Du,Andrew V Oleinikov

doi:10.3390/ijms21228755

Babak Mosavati, E Du + Show 1 more

Open Access

https://doi.org/10.3390/ijms21228755

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Abstract

The human placenta plays a key role in reproduction and serves as a major interface for maternofetal exchange of nutrients. Study of human placenta pathology presents a great experimental challenge because it is not easily accessible. In this paper, a 3D placenta-on-a-chip model is developed by bioengineering techniques to simulate the placental interface between maternal and fetal blood in vitro. In this model, trophoblasts cells and human umbilical vein endothelial cells are cultured on the opposite sides of a porous polycarbonate membrane, which is sandwiched between two microfluidic channels. Glucose diffusion across this barrier is analyzed under shear flow conditions. Meanwhile, a numerical model of the 3D placenta-on-a-chip model is developed. Numerical results of concentration distributions and the convection–diffusion mass transport is compared to the results obtained from the experiments for validation. Finally, effects of flow rate and membrane porosity on glucose diffusion across the placental barrier are studied using the validated numerical model. The placental model developed here provides a potentially helpful tool to study a variety of other processes at the maternal–fetal interface, for example, effects of drugs or infections like malaria on transport of various substances across the placental barrier.

Highlights

Placenta is a critical organ that supports embryonic growth by mediating, among other things, nutrient and oxygen supply to the fetus as well as removing waste products and carbon dioxide from the fetus [1,2,3]
We demonstrated an experimental-numerical strategy to evaluate a microfluidics-based placenta-on-a-chip model in the study of mass transport across the placental barrier
The results show that the glucose diffusion rate in co-culture cells model is smaller compared to monoculture and microdevice with no cells

Summary

Introduction

Placenta is a critical organ that supports embryonic growth by mediating, among other things, nutrient and oxygen supply to the fetus as well as removing waste products and carbon dioxide from the fetus [1,2,3]. Insufficient placental development may affect those functions and, in turn, increase mortality and morbidity of both fetus and mother. It has been shown that insufficient oxygen and nutrients transport across the placental barrier causes fetus adverse outcome [4]. Malarial infection in placenta during pregnancy, known as placental malaria, causes severe clinical conditions such as low birth weight [5], premature birth [6], intrauterine growth restriction [7], or abortion [8]. Studying diffusion efficiency across the placental barrier will provide a better understanding of the pathophysiological mechanisms involved in poor outcomes associated with diseases such as malaria infections in pregnancy. Study of human placental pathology remains a major experimental challenge as placenta is not accessible and highly species-specific on both host and pathogen sides, limiting the use of small animal models

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