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Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis.
Kanai, Ryo; Nakashima, Ayumu; Doi, Shigehiro; Kimura, Tomoe; Yoshida, Ken; Maeda, Satoshi; Ishiuchi, Naoki; Yamada, Yumi; Ike, Takeshi; Doi, Toshiki; Kato, Yukio; Masaki, Takao.
Affiliation
  • Kanai R; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Nakashima A; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan. ayumu@hiroshima-u.ac.jp.
  • Doi S; Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8553, Japan. ayumu@hiroshima-u.ac.jp.
  • Kimura T; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Yoshida K; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Maeda S; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Ishiuchi N; Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8553, Japan.
  • Yamada Y; TWOCELLS Company, Limited, 16-35 Hijiyama-honmachi, Minami-ku, Hiroshima, 732-0816, Japan.
  • Ike T; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Doi T; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Kato Y; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
  • Masaki T; Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
Sci Rep ; 11(1): 850, 2021 01 13.
Article de En | MEDLINE | ID: mdl-33441701
Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs' therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia-reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-ß1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Interféron gamma / Transplantation de cellules souches mésenchymateuses / Cellules souches mésenchymateuses / Maladies du rein Limites: Animals Langue: En Journal: Sci Rep Année: 2021 Type de document: Article Pays d'affiliation: Japon Pays de publication: Royaume-Uni

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Interféron gamma / Transplantation de cellules souches mésenchymateuses / Cellules souches mésenchymateuses / Maladies du rein Limites: Animals Langue: En Journal: Sci Rep Année: 2021 Type de document: Article Pays d'affiliation: Japon Pays de publication: Royaume-Uni