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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/17761

Title: Distinct spatial distribution of microglia and macrophages following mesenchymal stem cell implantation in mouse brain
Authors: Le Blon, Debbie
Hoornaert, Chloe
Daans, Jasmijn
SANTERMANS, Eva
HENS, Niel
Goossens, Herman
Berneman, Zwi
Ponsaerts, Peter
Issue Date: 2014
Publisher: NATURE PUBLISHING GROUP
Citation: IMMUNOLOGY AND CELL BIOLOGY, 92 (8), p. 650-658
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 CX(3)CR1(+/-) and CX(3)CR1(-/-) 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(+) CX(3)CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX(3)CR1(+) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX(3)CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX(3)CR1(+) 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.
Notes: [Le Blon, Debbie; Hoornaert, Chloe; Daans, Jasmijn; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Expt Cell Transplantat Grp, Lab Expt Hematol, B-2020 Antwerp, Belgium. [Le Blon, Debbie; Hoornaert, Chloe; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Vaccine & Infect Dis Inst Vaxinfectio, B-2020 Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, Ctr Stat, Diepenbeek, Belgium. [Hens, Niel] Univ Antwerp, Ctr Hlth Econ Res & Modeling Infect Dis, B-2020 Antwerp, Belgium.
URI: http://hdl.handle.net/1942/17761
DOI: 10.1038/icb.2014.49
ISI #: 000342376300076
ISSN: 0818-9641
Category: A1
Type: Journal Contribution
Validation: ecoom, 2015
Appears in Collections: Research publications

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