Haase Group

Engineering vascularised tissue-specific disease models

Externally funded projects

1. Development of a vascularized human placental barrier on-chip (MiVPChip, #PID2020-116745GA-I00)

Funding Body: Agencia Estatal de Investigación – Proyectos de I+D de GENERACIÓN DE CONOCIMIENTO

Project summary

The placenta acts as the primary source of nutrients and oxygen, as well as a first line of defence between fetus and exposure to toxic substances, bacteria and viruses from maternal blood. Models aimed at studying this unique organ typically include difficult-to-culture placental explants and animal models with mismatched placental physiology; thus, there is a strong need for the development of humanized in vitro tools. We have recently developed a model of fetal vasculature that demonstrated sensitivity to exogenous perfusion of inflammatory cytokines and perfusion with immune cells. This proposal aims to combine perfusable 3D fetal vessels with a stable trophoblast layer in order to generate a physiologic human placental interface system. Our model possesses the unique ability to perfuse both the maternal and fetal components, to distinctly regulate hemodynamics on-chip.

We aim to demonstrate a functional placental barrier – including resistance to transport of large proteins, and perfusion of small molecules (including hormones). We will employ the system to highlight key changes in both the secretome and transcriptome of fetal vasculature in response to anti-angiogenic markers upregulated in pre-eclampsia. Moreover, we will use our model to examine the understudied effect of pregnancy-specific glycoproteins (PSG-1) on the maternal-fetal interface, and examine their pro-angiogenic potential. The MiVPChip project aims to generate a human placental maternal-fetal interface on-chip, as a unique tool for investigating dysfunction of both the trophoblasts and vascular components of the placenta.  This model will provide insight into placental dysfunction and will serve as a platform to investigate xenobiotics transfer across the maternal-fetal interface.

Starting Date: 1st September 2021

Duration: 3 years