Trophoblast-derived factors drive human mesenchymal stem cell differentiation along an endothelial lineage: A model of early placental vasculogenesis

• DOI: 10.1016/j.repbio.2025.100994
• Publication Date: 2025-01-16T01:02:29Z
• Authors: Claire V. Harper; Leah Eccles; James Henstock; Jayne C. Charnock
• Keywords: Vasculogenesis; Trophoblast; Lineage (genetic)

Mechanisms controlling the process and patterning of blood vessel development in placenta remain largely unknown. The close physical proximity early vessels observed cytotrophoblast, as well reported production vasculogenic growth factors by latter, suggests that signalling between these two niches may be important. Here, we have developed an vitro model to address hypothesis secretion soluble factors, drives differentiation resident sub-trophoblastic mesenchymal stem cells (MSCs) along a vascular lineage, thereby establishing feto-placental circulation. BM-MSCs (a readily available for placental cells) were treated with conditioned medium containing secretome from human BeWo trophoblast cells, or endothelial (EGM2) supplemented exogenous (VEGF, IGF1 EGF) 10-12 days. Trophoblast-conditioned media, found contain detectable concentrations cytokines including VEGF, uPAR, TIMP-1, TIMP-2, IL6 factor, induced expression genes CD31, von Willibrand factor (vWF), FLT-1, VEGFR2 VE-Cadherin. Upregulation vWF protein was also detected following trophoblast-conditioned using immunocytochemistry. Wound healing (migration assay) Matrigel-tube formation assays confirmed cultured media exhibited functional measures addition expressing relevant markers. Identification key trophoblast-secreted their promotion helps advance our theories regarding relationship cell-cytotrophoblast niche coordinating complex angiogenic events occur placenta. presented here provides accessible reproducible tool further investigations into development.