Mesenchymal stem cells (MSCs) are well established to have promising therapeutic properties. TNF stimulated gene-6 (TSG-6), a potent tissue-protective and anti-inflammatory factor, has been demonstrated to be responsible for a significant part of the tissue-protecting properties mediated by MSCs. Nevertheless, current knowledge about the biological function of TSG-6 in MSCs is limited. Here, we demonstrated that TSG-6 is a crucial factor that influences many functional properties of MSCs. The transcriptomic sequencing analysis of wild-type (WT) and TSG-6−/−-MSCs shows that the loss of TSG-6 expression leads to the perturbation of several transcription factors, cytokines, and other key biological pathways. TSG-6−/−-MSCs appeared morphologically different with dissimilar cytoskeleton organization, significantly reduced size of extracellular vesicles, decreased cell proliferative rate, and loss of differentiation abilities compared with the WT cells. These cellular effects may be due to TSG-6-mediated changes in the extracellular matrix (ECM) environment. The supplementation of ECM with exogenous TSG-6, in fact, rescued cell proliferation and changes in morphology. Importantly, TSG-6-deficient MSCs displayed an increased capacity to release interleukin-6 conferring pro-inflammatory and pro-tumorigenic properties to the MSCs. Overall, our data provide strong evidence that TSG-6 is crucial for the maintenance of stemness and other biological properties of murine MSCs.

TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells / Romano, B; Elangovan, S; Erreni, M; Sala, E; Petti, L; Kunderfranco, P; Massimino, L; Restelli, S; Sinha, S; Lucchetti, D; Anselmo, A; Colombo, Fs; Stravalaci, M; Arena, V; D'Alessio, S; Ungaro, F; Inforzato, A; Izzo, Aa; Sgambato, A; Day, Aj; Vetrano, S.. - In: STEM CELLS. - ISSN 1066-5099. - 37:(2019), pp. 973-987. [10.1002/stem.3010]

TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells.

Romano B
Primo
;
Izzo AA;
2019

Abstract

Mesenchymal stem cells (MSCs) are well established to have promising therapeutic properties. TNF stimulated gene-6 (TSG-6), a potent tissue-protective and anti-inflammatory factor, has been demonstrated to be responsible for a significant part of the tissue-protecting properties mediated by MSCs. Nevertheless, current knowledge about the biological function of TSG-6 in MSCs is limited. Here, we demonstrated that TSG-6 is a crucial factor that influences many functional properties of MSCs. The transcriptomic sequencing analysis of wild-type (WT) and TSG-6−/−-MSCs shows that the loss of TSG-6 expression leads to the perturbation of several transcription factors, cytokines, and other key biological pathways. TSG-6−/−-MSCs appeared morphologically different with dissimilar cytoskeleton organization, significantly reduced size of extracellular vesicles, decreased cell proliferative rate, and loss of differentiation abilities compared with the WT cells. These cellular effects may be due to TSG-6-mediated changes in the extracellular matrix (ECM) environment. The supplementation of ECM with exogenous TSG-6, in fact, rescued cell proliferation and changes in morphology. Importantly, TSG-6-deficient MSCs displayed an increased capacity to release interleukin-6 conferring pro-inflammatory and pro-tumorigenic properties to the MSCs. Overall, our data provide strong evidence that TSG-6 is crucial for the maintenance of stemness and other biological properties of murine MSCs.
2019
TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells / Romano, B; Elangovan, S; Erreni, M; Sala, E; Petti, L; Kunderfranco, P; Massimino, L; Restelli, S; Sinha, S; Lucchetti, D; Anselmo, A; Colombo, Fs; Stravalaci, M; Arena, V; D'Alessio, S; Ungaro, F; Inforzato, A; Izzo, Aa; Sgambato, A; Day, Aj; Vetrano, S.. - In: STEM CELLS. - ISSN 1066-5099. - 37:(2019), pp. 973-987. [10.1002/stem.3010]
File in questo prodotto:
File Dimensione Formato  
Paper 33 Stem Cells 2019.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Accesso privato/ristretto
Dimensione 3.26 MB
Formato Adobe PDF
3.26 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/753310
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 33
social impact