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BioMed Research International
Volume 2014, Article ID 783459, 12 pages
http://dx.doi.org/10.1155/2014/783459
Research Article

SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

1Department of Biochemistry, Biophysics and General Pathology, Second University of Napoli, Via L. De Crecchio 7, 80138 Napoli, Italy
2Istituto Nazionale Tumori, Struttura Complessa Oncologia Medica Melanoma Immunoterapia Oncologica e Terapia Innovativa, Via Mariano Semmola, 80131 Napoli, Italy
3Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNR, Via P. Castellino 111, 80131 Napoli, Italy

Received 18 July 2014; Revised 7 August 2014; Accepted 8 August 2014; Published 27 August 2014

Academic Editor: Zongjin Li

Copyright © 2014 Botti Chiara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types. Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders. However, the molecular mechanisms underlying these effects remain unclear. A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function. Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions. Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level. We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level. Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis. Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs. Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.