TY - JOUR
T1 - Mouse Metanephric Mesenchymal Cell–Derived Angioblasts Undergo Vasculogenesis in Three-Dimensional Culture
AU - Patel, Mandakini
AU - Velagapudi, Chakradhar
AU - Burns, Hannah
AU - Doss, Robert
AU - Lee, Myung Ja
AU - Mariappan, Meenalakshmi M.
AU - Wagner, Brent
AU - Arar, Mazen
AU - Barnes, Veronique L.
AU - Abboud, Hanna E.
AU - Barnes, Jeffrey L.
N1 - Funding Information:
Supported by NIH/National Institute of Diabetes and Digestive and Kidney Disease Small Business Technology Transfer grant R42 DK077436 (J.L.B.), Small Business Innovation Research (SBIR) grants R44 DK061834 (V.L.B.), and R43 GM110837 (V.L.B.), and NIH grant R01 DK-102085 (B.W.), and the Veterans Administration Merit Review Program (J.L.B. and B.W.).
Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2017.10.022
DO - 10.1016/j.ajpath.2017.10.022
M3 - Article
C2 - 29269120
AN - SCOPUS:85042325777
SN - 0002-9440
VL - 188
SP - 768
EP - 784
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -