Blood lineage differentiation of placental villous core progenitors

Abstract

Background: In early pregnancy, placental macrophages (Hofbauer cells) and red blood cells (RBCs) are thought to arise de novo from specialised villus core progenitors, but little is understood about this process. Our prior work has identified two populations (CD31+/CD34+ placental endothelial progenitors and CD73+/CD90+ placental mesenchymal cells) that preliminary data suggest may be capable of generating macrophages or RBCs respectfully. Aim: This work aimed to better characterise placental villus core progenitors and identify potential sub-populations with phenotypic potential to give rise to haematopoietic lineages. Methods: First-trimester placentae (7-9 weeks of gestation) were collected and either sectioned for immunofluorescence staining of potential progenitor populations or denuded of trophoblast and enzymatically digested. Multicolour flow cytometry panels were utilised to either characterise villous core cells, sort potential progenitor populations, or characterise resulting cells following culture in haematopoietic differentiation media. Results: CD39+, CD144+, and CD73- sub-populations were identified within CD31+CD34+ endothelial cells and the sub-population expressing CD144 were further characterised an showed promise in having improved haematopoietic potential. A potential CD271+ population was also further characterised within CD73+CD90+ mesenchymal cells, suggesting improved haematopoietic potential. CD73+CD90+ mesenchymal cells were also preliminarily shown to give rise to cells expressing haematopoietic markers. Both CD73+CD90+ mesenchymal cells and CD31+CD34+CD144+ endothelial cells were localised to blood vessels within the placenta. FOLR2+HLA-DR- Hofbauer cells and FOLR2+HLA-DR+ maternal macrophages were characterised in the placenta and shown to have an M2 macrophage phenotype. Conclusion: this thesis characterised potential haematopoietic progenitors in the first trimester villous core in greater depth than has been undertaken previously. The sub-populations identified in this work are of interest for their potential ability to differentiate into haematopoietic lineages. Preliminary data suggests haematopoietic potential in culture which needs to be further assessed in vitro in future functional differentiation experiments.