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Title: A model of trophoblast development and implantation using human embryonic stem cells
Author: Udayashankar, Ramya
ISNI:       0000 0004 2676 9758
Awarding Body: The University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2009
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Abnormal embryo implantation may lead to poor fetal development and miscarriage, or pre-eclampsia. Due to ethical and practical restrictions, and the morphological diversity of implantation in laboratory animals, it is important to develop new in vitro models to study early events of human implantation. The aim of this study was to derive trophoblast stem cell lines from human embryonic stem cells (hESCs) through an effective repeatable protocol and to co-culture these cells together with an established endometrial cell culture system to develop and validate a model to study the molecular events of human embryo implantation. Derivation of trophoblast stem cell lines from hESC lines was established by spontaneous differentiation of embryoid bodies (EBs) and by initial measurement of human chorionic gonadotropin-{3 (hCG{3) secretion by enzyme linked immune sorbent assay (ELISA). The derived villous cytotrophoblast stem cell lines further differentiated to invasive, extra-villous cytotrophoblast cells; all cells lost their proliferative capacity and some lines acquired karyotypic changes, such as a gain in the X chromosome. Cell invasion assays confirmed that the extra-villous cytotrophoblast cells were invasive. When vesicles formed by aggregating trophoblast cells in suspension culture were co -cultured with decidualised human endometrial stromal cells in hypoxic (2% oxygen) and normoxic (20% oxygen) environments, erosion of the stromal layer in hypoxic conditions was observed similar to the embryo invasion through endometrium. To conclude, it has been possible to create trophoblast cell lines using human embryonic stem cells that differentiate and adapt in vitro and can be used as a model to study implantation in humans.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available