Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1.

Zanotti, L; Angioni, R; Calì, B; Soldani, C; Ploia, C; Moalli, Federica; Gargesha, M; D'Amico, G; Elliman, S; Tedeschi, G; Maffioli, E; Negri, A; Zacchigna, S; Sarukhan, A; Stein, Jens Volker; Viola, A (2016). Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1. Leukemia, 30(5), pp. 1143-1154. Nature Publishing Group 10.1038/leu.2016.33

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Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Moalli, Federica and Stein, Jens Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0887-6924

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

06 Jul 2016 10:46

Last Modified:

06 Jul 2016 10:46

Publisher DOI:

10.1038/leu.2016.33

PubMed ID:

26898191

BORIS DOI:

10.7892/boris.83983

URI:

https://boris.unibe.ch/id/eprint/83983

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