Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis

Tzuhua Lin, Jukka Pajarinen, Akira Nabeshima, Laura Lu, Karthik Nathan, Eemeli Jämsen, Zhenyu Yao, Stuart B. Goodman

研究成果: ジャーナルへの寄稿学術誌査読

55 被引用数 (Scopus)

抄録

BACKGROUND: Mesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation.

METHODS: In the current study, we developed a novel preconditioning strategy for MSCs using LPS plus TNF-α to optimize the immunomodulating ability of MSCs on macrophage polarization.

RESULTS: Preconditioned MSCs enhanced anti-inflammatory M2 macrophage marker expression (Arginase 1 and CD206) and decreased inflammatory M1 macrophage marker (TNF-α/IL-1Ra) expression using an in-vitro coculture model. Immunomodulation of MSCs on macrophages was significantly increased compared to the combination of IFN-γ plus TNF-α or single treatment controls. Increased osteogenic differentiation including alkaline phosphate activity and matrix mineralization was only observed in the LPS plus TNF-α preconditioned MSCs. Mechanistic studies showed that increased prostaglandin E2 (PGE2) production was associated with enhanced Arginase 1 expression. Selective cyclooxygenase-2 inhibition by Celecoxib decreased PGE2 production and Arginase 1 expression in cocultured macrophages.

CONCLUSIONS: The novel preconditioned MSCs have increased immunomodulation and bone regeneration potential and could be applied to the treatment of inflammatory bone disorders including periprosthetic osteolysis, fracture healing/nonunions, and osteonecrosis.

本文言語英語
論文番号277
ページ(範囲)277
ページ数1
ジャーナルStem cell research & therapy
8
1
DOI
出版ステータス出版済み - 12月 6 2017
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 分子医療
  • 生化学、遺伝学、分子生物学(その他)
  • 細胞生物学

フィンガープリント

「Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル