title: Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment.
abstract: Healing of skeletal defects is strictly dependent on osteogenesis and efficient vascularization of engineered scaffolds. Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) are both involved in these processes. The in vitro administration of IGF-1 in association with VEGF is able to modulate the osteoblastic or endothelial commitment of mesenchymal stromal cells (MSCs) of different origins (e.g. periosteum and skin). In the present study, in order to deepen a possible paracrine effect of IGF-1 and VEGF on periosteum-derived progenitor cells (PDPCs) and skin-derived MSCs (S-MSCs), a Transwell coculture approach was used. We explored the genes involved in endothelial and osteoblastic differentiation, those modulating mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase (PI3K)-AKT signaling pathways as well as genes implicated in stemness (i.e. Sox2, Oct4, and Nanog). Periosteal cells, which are typically committed toward osteoblastogenesis, are driven in the direction of endothelial gene expression when influenced by S-MSCs. The latter, once influenced by PDPCs, lose their endothelial commitment and increase the expression of osteoblast-associated genes. PI3K/AKT and MAPK signaling pathways seem to be markedly involved in this behavior. Our results evidence that paracrine signals between MSCs may differently modulate their commitment in a bone microenvironment, opening stimulating viewpoints for skeletal tissue engineering strategies coupling angiogenesis and osteogenesis processes.
authors.affiliation: Department of Clinical and Molecular Sciences, Universitx00E0; Politecnica delle Marche, Ancona, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Dicarlo
authors.forename: Novella
authors.initials: N
authors.lastname: Bianchi
authors.forename: Concetta
authors.initials: C
authors.lastname: Ferretti
authors.forename: Monia
authors.initials: M
authors.lastname: Orciani
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Primio
authors.forename: Monica
authors.initials: M
authors.lastname: Mattioli-Belmonte
mesh_terms: D000328:Adult; D019070:Cell Lineage / Q000187:drug effects*; D018920:Coculture Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects*; D010521:Periosteum / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I