title: Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide.
abstract: The immunoregulatory properties of mesenchymal stem cells (MSC) have been demonstrated on a wide range of cells. Here, we describe the modulatory effects of mouse bone marrow-derived MSC on BV2 microglia proliferation rate, nitric oxide (NO) production and CD40 expression. Mouse bone marrow MSC were co-cultured with BV2 cells at various seeding density ratios and activated with lipopolysaccharide (LPS). We show that MSC exert an anti-proliferative effect on microglia and are potent producers of NO when stimulated by soluble factors released by LPS-activated BV2. MSC suppressed proliferation of both untreated and LPS-treated microglia in a dose-dependent manner, significantly reducing BV2 proliferation at seeding density ratios of 1:0.2 and 1:0.1 (p<.05). Co-culturing MSC with BV2 cells at different ratios revealed interesting dynamics in NO production. A high number of MSC significantly increases NO in co-cultures whilst a lower number reduces NO. The increased NO levels in co-cultures may be MSC-derived, as we also show that activated BV2 cells stimulate MSC to produce NO. Cell-cell interaction is not a requirement for this effect as soluble factors released by activated BV2 cells alone do stimulate MSC to produce high levels of NO. Although NO is implicated as a mediator for T cell proliferation, it does not appear to play a major role in the suppression of microglia proliferation. Additionally, MSC reduced the expression of the microglial co-stimulator molecule, CD40. Collectively, these regulatory effects of MSC on microglia offer insight into the potential moderating properties of MSC on inflammatory responses within the CNS.
authors.affiliation: Immunology Laboratory, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400UPM Serdang, Selangor, Malaysia. yyin18@gmail.com
authors.forename: Yin Yin
authors.initials: YY
authors.lastname: Ooi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Zul'atfi
authors.initials: Z
authors.lastname: Rahmat
authors.forename: Hemavathy
authors.initials: H
authors.lastname: Subramaiam
authors.forename: Shi Wei
authors.initials: SW
authors.lastname: Tan
authors.forename: Maha
authors.initials: M
authors.lastname: Abdullah
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.forename: Sharmili
authors.initials: S
authors.lastname: Vidyadaran
mesh_terms: D000818:Animals; D001853:Bone Marrow; D019013:CD40 Antigens / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D019013:CD40 Antigens; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6; D009569:Nitric Oxide