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Biology subjects

James, J. L.

Publications and source records attributed to James, J. L..

2 recordsLinked to original sources

Multi-scale modelling of shear stress on the syncytiotrophoblast: Could maternal blood flow impact placental function across gestation?

The surface of the placenta is lined by a single multinucleated cell, the syncytiotrophoblast, which forms a functional barrier between maternal and fetal blood in pregnancy. The placenta plays a critical role in healthy fetal development and over the course of pregnancy forms a complex branching tree-like structure which bathes in maternal blood and serves a vital exchange function. It has been suggested that the structure of the placenta may evolve, in part, under the influence of the shear stress exerted by maternal blood flow over its surface, with the syncytiotrophoblast having a role in mechanosensing. However, data describing the mechano-sensitive nature of this cell, particularly in early gestation, is lacking. In this study we show that the syncytiotrophoblast expresses six proteins that have been related to shear sensing, and this expression is higher in the first trimester than at term. This suggests shear on the sycytiotrophoblast as an important factor influencing placental morphogenesis early in pregnancy. We then predict shear stress felt by the syncytiotrophoblast in first trimester and term placental tissue using a combination of porous medium modelling and explicit simulations of blood flow in realistic geometries derived from microCT imaging. Our models predict that typical shear stress on first-trimester tissue is higher than at term, supporting the feasibility of this mechanical stimulus as an important driver of healthy placental development.

bioengineering↗

The origins of placental mesenchymal stromal cells: Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae, and phenotypic convergence in culture

Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae.. Four distinct mesenchymal subsets were identified; CD73+CD90+ mesenchymal cells, CD146+CD271+ perivascular cells, podoplanin+CD36+ stromal cells, and CD26+CD90+ myofibroblasts. CD73+CD90+ and podoplanin+CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73+CD90+ cells and podoplanin+CD36+ cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73+CD90+CD31-CD144-CD45-). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplanin+CD36+ cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays.

cell biology↗