title: Distinct in vitro properties of embryonic and extraembryonic fibroblast-like cells are reflected in their in vivo behavior following grafting in the adult mouse brain.
abstract: Although intracerebral transplantation of various fibroblast(-like) cell populations has been shown feasible, little is known about the actual in vivo remodeling of these cellular grafts and their environment. In this study, we aimed to compare the in vitro and in vivo behavior of two phenotypically similar-but developmentally distinct-fibroblast-like cell populations, namely, mouse embryonic fibroblasts (mEFs) and mouse fetal membrane-derived stromal cells (mFMSCs). While both mEFs and mFMSCs are readily able to reduce TNF-α secretion by LPS/IFN-γ-activated BV-2 microglia, mFMSCs and mEFs display strikingly opposite behavior with regard to VEGF production under normal and inflammatory conditions. Whereas mFMSCs downregulate VEGF production upon coculture with LPS/IFN-γ-activated BV-2 microglia, mEFs upregulate VEGF production in the presence of LPS/IFN-γ-activated BV-2 microglia. Subsequently, in vivo grafting of mFMSCs and mEFs revealed no difference in microglial and astroglial responses toward the cellular grafts. However, mFMSC grafts displayed a lower degree of neoangiogenesis compared to mEF grafts, thereby potentially explaining the lower cell number able to survive in mFMSC grafts. In summary, our results suggest that physiological differences between fibroblast-like cell populations might lie at the basis of variations in histopathological and/or clinical outcome following cell grafting in mouse brain.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Costa
authors.forename: Irene
authors.initials: I
authors.lastname: Bergwerf
authors.forename: Eva
authors.initials: E
authors.lastname: Santermans
authors.forename: Nathalie
authors.initials: N
authors.lastname: De Vocht
authors.forename: Jelle
authors.initials: J
authors.lastname: Praet
authors.forename: Jasmijn
authors.initials: J
authors.lastname: Daans
authors.forename: Debbie
authors.initials: D
authors.lastname: Le Blon
authors.forename: Chloé
authors.initials: C
authors.lastname: Hoornaert
authors.forename: Kristien
authors.initials: K
authors.lastname: Reekmans
authors.forename: Niel
authors.initials: N
authors.lastname: Hens
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Ornella
authors.initials: O
authors.lastname: Parolini
authors.forename: Francesco
authors.initials: F
authors.lastname: Alviano
authors.forename: Peter
authors.initials: P
authors.lastname: Ponsaerts
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology*; D005321:Extraembryonic Membranes / Q000166:cytology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma