Flow in fetoplacental-like microvessels in vitro enhances perfusion, barrier function, and matrix stability

Area of Science:

• Reproductive Biology
• Vascular Biology
• Biomedical Engineering

Background:

• Placental vascularization is crucial for healthy pregnancy outcomes.
• Existing animal and explant models have limitations in accurately assessing human placental development.
• Understanding placental vascular development is key to addressing pregnancy complications.

Purpose of the Study:

• To develop and validate a novel 3D in vitro model of human placenta terminal villi.
• To investigate the effects of perfusable microvessels on placental tissue development and function.
• To establish a platform for studying shear stress effects on placental vasculature.

Main Methods:

• Co-culturing human umbilical vein endothelial cells (HUVEC), placental fibroblasts, and pericytes in a macrofluidic chip.
• Utilizing pressure-driven flow to promote microvessel growth and network formation.
• Employing computational fluid dynamics (CFD) and mass spectrometry for analysis.

Main Results:

• Successfully generated fully perfusable fetal microvessels forming stable, interconnected vascular networks.
• CFD simulations demonstrated that increased shear stress enhances microtissue stiffness and barrier function.
• Mass spectrometry identified flow-induced changes in protein expression, including matrix regulators and cytoskeleton-associated proteins.

Conclusions:

• The 3D placental microvessel model accurately mimics in vivo vascular development and response to flow.
• This model allows for the study of critical parameters like shear stress in placental vascularization.
• The platform shows significant potential for investigating the pathophysiology of pregnancy disorders linked to vascular dysfunction.