Mouse Metanephric Mesenchymal Cell–Derived Angioblasts Undergo Vasculogenesis in Three-Dimensional Culture

Mandakini Patel, Chakradhar Velagapudi, Hannah Burns, Robert Doss, Myung Ja Lee, Meenalakshmi M. Mariappan, Brent Wagner, Mazen Arar, Veronique L. Barnes, Hanna E. Abboud, Jeffrey L. Barnes

Research output: Contribution to journalArticlepeer-review

Abstract

In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB) cells grown in three-dimensional (3D) matrices formed organoids that consisted of primitive vascular structures surrounding a polarized epithelium. Here, we examined the potential of two principal effectors of vasculogenesis, vascular endothelial growth factor A (VEGF-A), and platelet-derived growth factor B chain (PDGF-BB), to stimulate MM cell differentiation. The results showed that MM cells possess angioblast characteristics by expressing phenotypic markers for endothelial and mesenchymal cells. UB cells synthesize VEGF-A and PDGF-BB proteins and RNA, whereas the MM cells express the respective cognate receptors, supporting their role in directional induction of vasculogenesis. VEGF-A stimulated proliferation of MM cells in monolayer and in 3D sponges but did not affect MM cell migration, organization, or vasculogenesis. However, PDGF-BB stimulated MM cell proliferation, migration, and vasculogenesis in monolayer and organization of the cells into primitive capillary-like assemblies in 3D sea sponge scaffolds in vitro. A role for PDGF-BB in vasculogenesis in the 3D MM/UB co-culture system was validated by direct interference with PDGF-BB or PDGF receptor-β cell interactions to implicate PDGF-BB as a primary effector of MM cell vasculogenesis. Thus, MM cells resemble early renal angioblasts that may provide an ideal platform for the investigation of renal vasculogenesis in vitro.

Original languageEnglish (US)
Pages (from-to)768-784
Number of pages17
JournalAmerican Journal of Pathology
Volume188
Issue number3
DOIs
StatePublished - Mar 2018

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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