Faculty
Schulich School of Medicine and Dentistry
Supervisor Name
Peeyush Lala
Keywords
human placenta, spheroid, trophoblast, endometrial stromal cell, trophoblast stem cell
Description
The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We formed spheroids with HTR-8/SVneo trophoblasts (HTRs) and telomere-immortalized human endometrial stromal cells (THESCs), which were then apposed to one another. When observed for 24 hours, HTR and THESC spheroids did not replicate trophoblast invasion of the endometrial stroma. Human trophoblast stem cells (hTSCs) are another promising cell line that can be directed toward all trophoblast lineages. Currently, we are working to characterize the trophoblast subpopulations and matrix markers in hTSC spheroids. We anticipate that comparing HTR and hTSC spheroids, incorporating all trophoblast subpopulations within a single spheroid, and refining the apposition of spheroids would result in a more sophisticated in vitro 3D placental model. Based on previous work in our laboratory, genetically manipulated THESCs could generate diseased phenotypes of hypo-invasive or hyper-invasive placentas. While the complex structure of the placenta cannot be entirely reproduced in vitro, our work lays the background for constructing placentas in health and disease.
Acknowledgements
This project was generously supported by CIHR and NSERC grants to Dr. Peeyush K. Lala. We would also like to thank Mariyan J. Jeyarajah, Stephen J. Renaud, all other members of the Lala and Renaud Labs, and Lin Zhao from the Whitehead Lab for their expertise and guidance.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Document Type
Poster
Constructing an In Vitro 3D Model of the Human Placenta
The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We formed spheroids with HTR-8/SVneo trophoblasts (HTRs) and telomere-immortalized human endometrial stromal cells (THESCs), which were then apposed to one another. When observed for 24 hours, HTR and THESC spheroids did not replicate trophoblast invasion of the endometrial stroma. Human trophoblast stem cells (hTSCs) are another promising cell line that can be directed toward all trophoblast lineages. Currently, we are working to characterize the trophoblast subpopulations and matrix markers in hTSC spheroids. We anticipate that comparing HTR and hTSC spheroids, incorporating all trophoblast subpopulations within a single spheroid, and refining the apposition of spheroids would result in a more sophisticated in vitro 3D placental model. Based on previous work in our laboratory, genetically manipulated THESCs could generate diseased phenotypes of hypo-invasive or hyper-invasive placentas. While the complex structure of the placenta cannot be entirely reproduced in vitro, our work lays the background for constructing placentas in health and disease.