Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide.
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.
Ooi
Yin Yin
YY
Immunology Laboratory, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400UPM Serdang, Selangor, Malaysia. yyin18@gmail.com
Ramasamy
Rajesh
R
Rahmat
Zul'atfi
Z
Subramaiam
Hemavathy
H
Tan
Shi Wei
SW
Abdullah
Maha
M
Israf
Daud Ahmad
DA
Vidyadaran
Sharmili
S
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
D019013:CD40 Antigens; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6; D009569:Nitric Oxide