Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α

Yi Liu, Lei Wang, Takashi Kikuiri, Kentaro Akiyama, Chider Chen, Xingtian Xu, Ruili Yang, Wan Jun Chen, Songlin Wang, Songtao Shi

Research output: Contribution to journalArticle

359 Citations (Scopus)

Abstract

Stem cell-based regenerative medicine is a promising approach in tissue reconstruction. Here we show that proinflammatory T cells inhibit the ability of exogenously added bone marrow mesenchymal stem cells (BMMSCs) to mediate bone repair. This inhibition is due to interferon γ (IFN-γ)-induced downregulation of the runt-related transcription factor 2 (Runx-2) pathway and enhancement of tumor necrosis factor α (TNF-α) signaling in the stem cells. We also found that, through inhibition of nuclear factor κB (NF-κB), TNF-α converts the signaling of the IFN-γ-activated, nonapoptotic form of TNF receptor superfamily member 6 (Fas) in BMMSCs to a caspase 3- and caspase 8-associated proapoptotic cascade, resulting in the apoptosis of these cells. Conversely, reduction of IFN-γ and TNF-α concentrations by systemic infusion of Foxp3 + regulatory T cells, or by local administration of aspirin, markedly improved BMMSC-based bone regeneration and calvarial defect repair in C57BL/6 mice. These data collectively show a previously unrecognized role of recipient T cells in BMMSC-based tissue engineering.

Original languageEnglish
Pages (from-to)1594-1601
Number of pages8
JournalNature Medicine
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Liu, Y., Wang, L., Kikuiri, T., Akiyama, K., Chen, C., Xu, X., Yang, R., Chen, W. J., Wang, S., & Shi, S. (2011). Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nature Medicine, 17(12), 1594-1601. https://doi.org/10.1038/nm.2542