title: Human placental multipotent mesenchymal stromal cells modulate placenta angiogenesis through Slit2-Robo signaling.
abstract: The objective of this study was to investigate whether human placental multipotent mesenchymal stromal cell (hPMSC)-derived Slit2 and endothelial cell Roundabout (Robo) receptors are involved in placental angiogenesis. The hPMSC-conditioned medium and human umbilical vein endothelial cells were studied for Slit2 and Robo receptor expression by immunoassay and RT-PCR. The effect of the conditioned medium of hPMSCs with or without Slit2 depletion on endothelial cells was investigated by in vitro angiogenesis using growth factor-reduced Matrigel. hPMSCs express Slit2 and both Robo1 and Robo4 are present in human umbilical vein endothelial cells. Human umbilical vein endothelial cells do not express Robo2 and Robo3. The hPMSC-conditioned medium and Slit2 recombinant protein significantly inhibit the endothelial cell migration, but not by the hPMSC-conditioned medium with Slit2 depletion. The hPMSC-conditioned medium and Slit2 significantly enhance endothelial tube formation with increased cumulated tube length, polygonal network number and vessel branching point number compared to endothelial cells alone. The tube formation is inhibited by the depletion of Slit2 from the conditioned medium, or following the expression of Robo1, Robo4, and both receptor knockdown using small interfering RNA. Furthermore, co-immunoprecipitation reveals Slit2 binds to Robo1 and Robo4. Robo1 interacts and forms a heterodimeric complex with Robo4. These results suggest the implication of both Robo receptors with Slit2 signaling, which is involved in endothelial cell angiogenesis. Slit2 in the conditioned medium of hPMSCs has functional effect on endothelial cells and may play a role in placental angiogenesis.
authors.affiliation: a Department of Medical Research , MacKay Memorial Hospital , Taipei , Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: b Division of High Risk Pregnancy, MacKay Memorial Hospital , Taipei , Taiwan.
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: a Department of Medical Research , MacKay Memorial Hospital , Taipei , Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: a Department of Medical Research , MacKay Memorial Hospital , Taipei , Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Wu
authors.affiliation: a Department of Medical Research , MacKay Memorial Hospital , Taipei , Taiwan.|b Division of High Risk Pregnancy, MacKay Memorial Hospital , Taipei , Taiwan.
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
mesh_terms: D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply* / Q000166:cytology; D011247:Pregnancy; D055503:Protein Multimerization / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C462951:ROBO4 protein, human
keywords: Robo; Slit2; angiogenesis; endothelial cells; placental multipotent mesenchymal stromal cells