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, WanJun Chen, Songlin Wang, Songtao Shi

Research output: Contribution to journalArticle

332 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 2011
Externally publishedYes

Fingerprint

Tissue regeneration
T-cells
Stem cells
Mesenchymal Stromal Cells
Interferons
Regeneration
Bone
Tumor Necrosis Factor-alpha
Bone Marrow
T-Lymphocytes
Stem Cells
Bone Regeneration
Regenerative Medicine
Caspase 8
Tumor Necrosis Factor Receptors
Repair
Regulatory T-Lymphocytes
Tissue Engineering
Inbred C57BL Mouse
Caspase 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. / Liu, Yi; Wang, Lei; Kikuiri, Takashi; Akiyama, Kentaro; Chen, Chider; Xu, Xingtian; Yang, Ruili; Chen, WanJun; Wang, Songlin; Shi, Songtao.

In: Nature Medicine, Vol. 17, No. 12, 12.2011, p. 1594-1601.

Research output: Contribution to journalArticle

Liu, Y, Wang, L, Kikuiri, T, Akiyama, K, Chen, C, Xu, X, Yang, R, Chen, W, 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, vol. 17, no. 12, pp. 1594-1601. https://doi.org/10.1038/nm.2542
Liu, Yi ; Wang, Lei ; Kikuiri, Takashi ; Akiyama, Kentaro ; Chen, Chider ; Xu, Xingtian ; Yang, Ruili ; Chen, WanJun ; Wang, Songlin ; Shi, Songtao. / Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. In: Nature Medicine. 2011 ; Vol. 17, No. 12. pp. 1594-1601.
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