| First Author | Liu Y | Year | 2011 |
| Journal | Nat Med | Volume | 17 |
| Issue | 12 | Pages | 1594-601 |
| PubMed ID | 22101767 | Mgi Jnum | J:180364 |
| Mgi Id | MGI:5306167 | Doi | 10.1038/nm.2542 |
| Citation | Liu Y, et al. (2011) Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha. Nat Med 17(12):1594-601 |
| abstractText | 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 gamma (IFN-gamma)-induced downregulation of the runt-related transcription factor 2 (Runx-2) pathway and enhancement of tumor necrosis factor alpha (TNF-alpha) signaling in the stem cells. We also found that, through inhibition of nuclear factor kappaB (NF-kappaB), TNF-alpha converts the signaling of the IFN-gamma-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-gamma and TNF-alpha 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. |
