Tissue-engineered multi-cellular models of the uterine wall
- PDF / 2,310,853 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 37 Downloads / 167 Views
ORIGINAL PAPER
Tissue‑engineered multi‑cellular models of the uterine wall Tatyana Kuperman1 · Mark Gavriel1 · Ruth Gotlib1 · Ying Zhang2 · Ariel Jaffa3,5 · David Elad1 · Dan Grisaru4,5 Received: 28 September 2019 / Accepted: 21 January 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The human uterus is composed of three layers: endometrium, myometrium and perimetrium. It remodels during the monthly menstrual cycle and more significantly during the complex stages of reproduction. In vivo studies of the human uterine wall are yet incomplete due to ethical and technical limitations. The objective of this study was to develop in vitro uterine wall models that mimic the in vivo structure in humans. We co-cultured multiple cellular models of endometrial epithelial cells, endometrial stromal cells and smooth muscle cells on a synthetic membrane mounted in multi-purpose custom-designed wells. Immunofluorescence staining and confocal imaging confirmed that the new model represents the in vivo anatomical architecture of the inner uterine wall. Hormonal treatment with progesterone and β-estradiol demonstrated increased expression of progestogen-associated endometrial protein, which is associated with the in vivo receptive uterus. The new tissue-engineered in vitro models of the uterine wall will enable deeper investigation of molecular and biomechanical aspects of the blastocyst–uterus interaction during the window of implantation. Keywords In vitro model · Multi-cellular co-culture · Progesterone · β-Estradiol · Receptive uterus · Custom-designed well
1 Introduction The human uterine wall is composed of three layers: the inner endometrium, the middle myometrium and the outer perimetrium. The structural architecture of the endometrium and myometrium undergoes different remodeling procedures to accommodate the important reproductive stages. First, generation of uterine peristalsis that transports the sperm to the fallopian tube and then transport of the blastocyst to the implantation site. The next stages include the blastocyst implantation into the endometrium, development of the * David Elad [email protected] 1
Department of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, 69978 Tel‑Aviv, Israel
2
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3
Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel-Aviv Medical Center, 64239 Tel‑Aviv, Israel
4
Gynecological Oncology Unit, Lis Maternity Hospital, Tel-Aviv Medical Center, 64239 Tel‑Aviv, Israel
5
Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel
placenta and accommodation of the fetus during gestation, and lastly, delivery of the fetus and the placenta. A huge volume of knowledge has already been developed on the molecular activities during these stages in different mammalian species, but very little in humans due to ethical and technical restrictions. Given the quantitative and qua
Data Loading...
