title: Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders.
abstract: The central nervous system (CNS) is a very unique system with multiple features that differentiate it from systemic tissues. One of the most captivating aspects of its distinctive nature is the presence of the blood brain barrier (BBB), which seals it from the periphery. Therefore, to preserve tissue homeostasis, the CNS has to rely heavily on resident cells such as microglia. These pivotal cells of the mononuclear lineage have important and dichotomous roles according to various neurological disorders. However, certain insults can overwhelm microglia as well as compromising the integrity of the BBB, thus allowing the infiltration of bone marrow-derived macrophages (BMDMs). The use of myeloablation and bone marrow transplantation allowed the generation of chimeric mice to study resident microglia and infiltrated BMDM separately. This breakthrough completely revolutionized the way we captured these 2 types of mononuclear phagocytic cells. We now realize that microglia and BMDM exhibit distinct features and appear to perform different tasks. Since these cells are central in several pathologies, it is crucial to use chimeric mice to analyze their functions and mechanisms to possibly harness them for therapeutic purpose. This review will shed light on the advent of this methodology and how it allowed deciphering the ontology of microglia and its maintenance during adulthood. We will also compare the different strategies used to perform myeloablation. Finally, we will discuss the landmark studies that used chimeric mice to characterize the roles of microglia and BMDM in several neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center, Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Larochelle
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center, Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Bellavance
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center, Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Michaud
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center, Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Québec G1V 4G2, Canada. Electronic address: Serge.Rivest@crchudequebec.ulaval.ca.
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009422:Nervous System Diseases / Q000235:genetics / Q000473:pathology*
keywords: Alzheimer's disease; Bone marrow; Chimeric mice; Multiple sclerosis; Myeloid cells; Stroke