Souza Glauco R, Tseng Hubert, Gage Jacob A, Mani Arunmani, Desai Pujan, Leonard Fransisca, Liao Angela, Longo Monica, Refuerzo Jerrie S, Godin Biana
Nano3D Biosciences, Houston, TX 77030, USA.
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Int J Mol Sci. 2017 Mar 23;18(4):683. doi: 10.3390/ijms18040683.
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.
子宫收缩调节异常可导致女性生殖系统常见的病理紊乱，包括早产、不孕、着床异常和月经周期不规律。更好地了解人类子宫肌层收缩对于设计和测试针对这些重要临床问题的干预措施至关重要。对人类子宫收缩生理学进行有力研究需要利用人类来源的体外模型。重要的是，子宫收缩是一种三维协调现象，应在三维环境中进行研究。在此，我们首次提出并评估一种用于评估人类子宫收缩的三维体外模型。应用磁性三维生物打印技术将人类子宫肌层细胞排列成环，然后随时间以及作为各种临床相关药物的函数监测其收缩性。将市售的和患者来源的子宫肌层细胞以384孔板形式磁性生物打印成环，用于高通量子宫收缩性分析。来自不同细胞来源和患者的生物打印子宫环显示出不同的收缩模式，并且对临床相关的子宫收缩抑制剂吲哚美辛和硝苯地平有不同反应。我们相信，这个新系统将成为评估人类分娩生理学的有用工具，同时能够对多种药物和条件进行高通量测试。
