title: Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.
abstract: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Juan
authors.identifier: 0000-0003-3999-0841
authors.initials: J
authors.lastname: Bayo
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Esteban
authors.identifier: 0000-0003-1059-1695
authors.initials: E
authors.lastname: Fiore
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina ; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina.
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Aquino
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Malvicini
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Manglio
authors.identifier: 0000-0003-2829-4701
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Estanislao
authors.identifier: 0000-0001-5226-9747
authors.initials: E
authors.lastname: Peixoto
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina ; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina.
authors.forename: Laura
authors.identifier: 0000-0002-6070-6078
authors.initials: L
authors.lastname: Alaniz
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina.
authors.forename: Flavia
authors.identifier: 0000-0003-0685-9927
authors.initials: F
authors.lastname: Piccioni
authors.affiliation: CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina ; Laboratorio de Terapia Molecular y Celular, Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Bolontrade
authors.affiliation: CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina ; Laboratorio de Terapia Molecular y Celular, Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Podhajcer
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina ; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Garcia
authors.affiliation: Laboratorio de Terapia Génica, Facultad de Ciencias Biomédicas, Universidad Austral, B1629ODT Derqui-Pilar, Buenos Aires, Argentina ; CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), C1033AAJ Buenos Aires, Argentina ; Unidad de Hígado, Hospital Universitario Austral, Universidad Austral, B1629ODT Derqui-Pilar, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism; D051243:Caveolin 2 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D060285:Receptors, Autocrine Motility Factor / Q000378:metabolism*; D014470:Umbilical Cord / Q000378:metabolism / Q000473:pathology*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D017077:Culture Media, Conditioned; D060285:Receptors, Autocrine Motility Factor; D019278:Matrix Metalloproteinase 3