Abstract
Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions.
Highlights
The uterus is an organ of the female reproductive system
Robust studies to better understand the physiology of human uterine contractions cannot be performed in vivo and require in vitro models, which utilize human source
We proposed and evaluated a 3D cell culture platform that could potentially overcome the above limitations to build a uterine contractility assay, which is based on magnetic 3D bioprinting [28,29,30,31]
Summary
The uterus is an organ of the female reproductive system. It is a hollow organ and has three main layers: a well-differentiated endometrium lining, a thick smooth muscle, known as “myometrium”, and an outer serosal layer [1,2,3]. A variety of different 3D cell culture platforms exist: protein gels, such as Matrigel® (BD Biosciences, San Jose, CA, USA) and collagen that recreate ECM composition [19]; polymer scaffolds that reproduce tissue structure and material properties [20]; hanging drop spheroids that use water tension in liquid droplets to aggregate cells into spheroids [21,22]; round bottom plates that use plate geometry to aggregate cells in spherical bottom wells [23]; and nano-patterned plates, with wells
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