Open AccessTNF‐Stimulated Gene‐6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells
Author(s) -
Romano Barbara,
Elangovan Sudharshan,
Erreni Marco,
Sala Emanuela,
Petti Luciana,
Kunderfranco Paolo,
Massimino Luca,
Restelli Silvia,
Sinha Shruti,
Lucchetti Donatella,
Anselmo Achille,
Colombo Federico Simone,
Stravalaci Matteo,
Arena Vincenzo,
D'Alessio Silvia,
Ungaro Federica,
Inforzato Antonio,
Izzo Angelo A.,
Sgambato Alessandro,
Day Anthony J.,
Vetrano Stefania
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3010
Subject(s) - mesenchymal stem cell , biology , microbiology and biotechnology , extracellular matrix , stem cell , transcription factor , regulator , gene , genetics
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.