Stem cell insights into human trophoblast lineage differentiation

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Show simple item record Gamage, Teena en Chamley, Lawrence en James, Joanna en 2017-03-03T03:23:49Z en 2016-12-01 en
dc.identifier.citation Human Reproduction Update 23(1):77-103 01 Dec 2016 en
dc.identifier.issn 1355-4786 en
dc.identifier.uri en
dc.description.abstract BACKGROUND: The human placenta is vital for fetal development, yet little is understood about how it forms successfully to ensure a healthy pregnancy or why this process is inadequate in 1 in 10 pregnancies, leading to miscarriage, intrauterine growth restriction or preeclampsia. Trophoblasts are placenta-specific epithelial cells that maximize nutrient exchange. All trophoblast lineages are thought to arise from a population of trophoblast stem cells (TSCs). However, whilst the isolation of murine TSC has led to an explosion in understanding murine placentation, the isolation of an analogous human TSC has proved more difficult. Consequently, alternative methods of studying human trophoblast lineage development have been employed, including human embryonic stem cells (hESCs), induced pluripotent stem cells (iPS) and transformed cell lines; but what do these proxy models tell us about what is happening during early placental development? OBJECTIVE AND RATIONALE: In this systematic review, we evaluate current approaches to understanding human trophoblast lineage development in order to collate and refine these models and inform future approaches aimed at establishing human TSC lines. SEARCH METHODS: To ensure all relevant articles were analysed, an unfiltered search of Pubmed, Embase, Scopus and Web of Science was conducted for 25 key terms on the 13th May 2016. In total, 47 313 articles were retrieved and manually filtered based on non-human, non-English, non-full text, non-original article and off-topic subject matter. This resulted in a total of 71 articles deemed relevant for review in this article. OUTCOMES: Candidate human TSC populations have been identified in, and isolated from, both the chorionic membrane and villous tissue of the placenta, but further investigation is required to validate these as 'true' human TSCs. Isolating human TSCs from blastocyst trophectoderm has not been successful in humans as it was in mice, although recently the first reported TSC line (USFB6) was isolated from an eight-cell morula. In lieu of human TSC lines, trophoblast-like cells have been induced to differentiate from hESCs and iPS. However, differentiation in these model systems is difficult to control, culture conditions employed are highly variable, and the extent to which they accurately convey the biology of 'true' human TSCs remains unclear, particularly as a consensus has not been met among the scientific community regarding which characteristics a human TSC must possess. WIDER IMPLICATIONS: Human TSC models have the potential to revolutionize our understanding of trophoblast differentiation, allowing us to make significant gains in understanding the underlying pathology of pregnancy disorders and to test potential therapeutic interventions on cell function in vitro. In order to do this, a collaborative effort is required to establish the criteria that define a human TSC to confirm the presence of human TSCs in both primary isolates and to determine how accurately trophoblast-like cells derived from current model systems reflect trophoblast from primary tissue. The in vitro systems currently used to model early trophoblast lineage formation have provided insights into early human placental formation but it is unclear whether these trophoblast-like cells are truly representative of primary human trophoblast. Consequently, continued refinement of current models, and standardization of culture protocols is essential to aid our ability to identify, isolate and propagate 'true' human TSCs from primary tissue. en
dc.publisher Oxford University Press en
dc.relation.ispartofseries Human Reproduction Update en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Stem cell insights into human trophoblast lineage differentiation en
dc.type Journal Article en
dc.identifier.doi 10.1093/humupd/dmw026 en
pubs.issue 1 en
pubs.begin-page 77 en
pubs.volume 23 en
dc.rights.holder Copyright: Oxford University Press en
dc.identifier.pmid 27591247 en
pubs.end-page 103 en
pubs.publication-status Published online en
dc.rights.accessrights en
pubs.subtype Review en
pubs.elements-id 541260 en Medical and Health Sciences en Medical Sciences en Physiology Division en School of Medicine en Obstetrics and Gynaecology en
dc.identifier.eissn 1460-2369 en
pubs.record-created-at-source-date 2017-03-03 en 2016-09-02 en
pubs.dimensions-id 27591247 en

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