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

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number277
Pages (from-to)277
Number of pages1
JournalStem cell research & therapy
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 6 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Fingerprint Dive into the research topics of 'Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis'. Together they form a unique fingerprint.

Cite this