title: Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor (VEGFR-3) in the glial reaction elicited by human mesenchymal stem cell engraftment in the normal rat brain.
abstract: To determine whether vascular endothelial growth factor-C (VEGF-C) and its receptor (VEGFR-3) are involved in the glial reaction elicited by transplanted mesenchymal stem cells (MSCs), we examined the cellular localization of VEGF-C and VEGFR-3 proteins in the striatum of adult normal rats that received bone marrow-derived human MSCs. The MSC grafts were infiltrated with activated microglia/macrophages and astrocytes over a 2-week period post-transplantation, which appeared to parallel the loss of transplanted MSCs. VEGF-C/VEGFR-3 was expressed in activated microglia/macrophages recruited to the graft site, where the induction of VEGF-C protein was rather late compared with that of its receptor. VEGF-C protein was absent or very weak on day 3, whereas VEGFR-3 immunoreactivity was evident within the first three days. Furthermore, within three days, VEGF-C could be detected in the brain macrophages localized immediately adjacent to the needle track. At the same time, almost all the brain macrophages in both regions expressed VEGFR-3. Reactive astrocytes at the graft site expressed VEGFR-3, but not VEGF-C. These data demonstrated the characteristic time- and cell-dependent expression patterns for VEGF-C and VEGFR-3 within the engrafted brain tissue, suggesting that they may contribute to neuroinflammation in MSC transplantation, possibly through the recruitment and/or activation of microglia/macrophages and astrogliosis.
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea (YJS, TRR, JHP, HJP, MYL).
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea (YJS, TRR, JHP, HJP, MYL).
authors.forename: Tae-Ryong
authors.initials: TR
authors.lastname: Riew
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea (YJS, TRR, JHP, HJP, MYL).
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea (YJS, TRR, JHP, HJP, MYL).
authors.forename: Ha-Jin
authors.initials: HJ
authors.lastname: Pak
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea (YJS, TRR, JHP, HJP, MYL).
authors.forename: Mun-Yong
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis* / Q000276:immunology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis* / Q000276:immunology
chemical_list: D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Astrocytes; Brain macrophages; Cell transplantation; Mesenchymal stem cells; VEGF-C; VEGFR-3