New Publication: A Human-Based Laboratory Model to Study Uterine Cell Contractions in Pregnancy

Identifying Mechano-Modulators of Myometrial Contractility in a Scalable Hydrogel Culture Platform

Isabella C. Claure, PhD, Catherine M. Klapperich, PhD, and Joyce Y. Wong, PhD

In this work, we set out to address a critical problem in pregnancy care: abnormal uterine contractions that cause complications like preterm birth and postpartum hemorrhage. Currently, drugs to control these contractions are nonspecific and often ineffective. A major barrier to studying this problem in vitro (outside of the body) is that myometrial cells (uterine smooth muscle cells) are usually studied on very stiff plastic, which does not resemble the true mechanical environment of the uterus.

To address this problem, we developed a simple, scalable hydrogel system in standard lab plates that lets us tune stiffness to mimic healthy, diseased, and non-physiologic conditions. We used this system to measure how myometrial cells respond to oxytocin (a hormone that stimulates contractions in labor) by tracking calcium signals from the cells. We found that both matrix stiffness and inflammatory cues, such as LPS, significantly alter these oxytocin-driven calcium responses, and that conventional rigid plastic can distort cell shape and signaling. By creating a more realistic human-based laboratory model, a new approach methodology (NAM) , we aim to enable better testing of drugs that modulate uterine contractions and ultimately improve treatments for pregnancy-related complications.