title: Mesenchymal stem cell transplantation modulates neuroinflammation in focal cerebral ischemia: contribution of fractalkine and IL-5.
abstract: Mesenchymal stem cells (MSCs) are reported to possess immunomodulatory properties. Previous reports have demonstrated the beneficial effects of MSC-transplantation in focal cerebral ischemia animal models. In this study, we have investigated the neuroimmunomodulatory functions of human MSCs, transplanted in a rat focal ischemia model of transient middle cerebral artery occlusion (MCAO). Our results revealed that in a human mesenchymal stem cell line, B10 cell transplantation decreased the accumulation of Iba-1(+) microglia and GFAP(+) astrocytes, and inhibited proinflammatory gene expression in the core and ischemic border zone (IBZ). Among the proinflammatory genes iNOS, which was expressed in microglia/macrophage, was persistently inhibited up to 7days after MCAO. In vivo laser capture microdissection and double immunofluorescence staining, and in vitro B10 cell culture experiments showed that, in inflammatory conditions, B10 cells expressed cytokines and growth factors including IL-5, fractalkine, IGF-1, GDNF and VEGF. Fractalkine and IL-5 inhibited cytokine-induced proinflammatory gene expression including iNOS in a human microglia cell line. Thus, our results demonstrate that MSC transplantation suppresses MCAO focal ischemia-induced inflammation, possibly through expression of fractalkine and IL-5.
authors.affiliation: Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Abdullah Md
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.forename: Kiryo
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Dashdemberel
authors.initials: D
authors.lastname: Narantuya
authors.forename: Shotai
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D002460:Cell Line; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D015848:Interleukin-5 / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054428:Chemokine CX3CL1; D015848:Interleukin-5