title: Distinct spatial distribution of microglia and macrophages following mesenchymal stem cell implantation in mouse brain.
abstract: Although implantation of cellular material in the central nervous system (CNS) is a key direction in CNS regenerative medicine, this approach is currently limited by the occurrence of strong endogenous immune cell responses. In a model of mesenchymal stem cell (MSC) grafting in the CNS of immune-competent mice, we previously described that MSC grafts become highly surrounded and invaded by Iba1(+) myeloid cells (microglia and/or macrophages). Here, following grafting of blue fluorescent protein (BFP)-expressing MSC in the CNS of CX3CR1(+/-) and CX3CR1(-/-) mice, our results indicate: (1) that the observed inflammatory response is independent of the fractalkine signalling axis, and (2) that a significant spatial distribution of Iba1(+) inflammatory cells occurs, in which Iba1(+) CX3CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX3CR1(-) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX3CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX3CR1(-) myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, we performed MSC-BFP grafting experiments in the CNS of eGFP(+) bone marrow chimeric C57BL/6 mice. Analysis of MSC-BFP grafts in the CNS of these mice confirmed our observation that peripheral monocytes/macrophages invade the MSC graft and that resident microglia surround the MSC graft site. Furthermore, analysis of major histocompatibility complex class II (MHCII) expression revealed that mainly macrophages, but not microglia, express this M1 pro-inflammatory marker in the context of MSC grafting in the CNS. These results again highlight the complexity of cell implantation immunology in the CNS.
authors.affiliation: 1] Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium [2] Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Debbie
authors.initials: D
authors.lastname: Le Blon
authors.affiliation: 1] Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium [2] Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Chloé
authors.initials: C
authors.lastname: Hoornaert
authors.affiliation: 1] Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium [2] Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Jasmijn
authors.initials: J
authors.lastname: Daans
authors.affiliation: Center for Statistics, I-Biostat, Hasselt University, Diepenbeek, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Santermans
authors.affiliation: 1] Center for Statistics, I-Biostat, Hasselt University, Diepenbeek, Belgium [2] Centre for Health Economic Research and Modeling Infectious Diseases (Chermid), University of Antwerp, Antwerp, Belgium.
authors.forename: Niel
authors.initials: N
authors.lastname: Hens
authors.affiliation: Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: 1] Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium [2] Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.affiliation: 1] Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium [2] Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Ponsaerts
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic; D018183:Transplantation Chimera
chemical_list: C491049:Aif1 protein, mouse; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV