Zebrafish embryo extract counteracts human stem cell senescence

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Article

Federica Facchin^1,5, Silvia Canaider^1,5, Eva Bianconi^1,5, Margherita Maioli^2,6,7, Umberto Santoro³, Sara Santaniello², Valentina Basoli^2,8,9, Pier Mario Biava⁴, Carlo Ventura^1,5,*

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¹ Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy

² Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy

³ Medical Technology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano, 1/10, 40136 Bologna, Italy

⁴ Scientific Institute of Research and Care Multimedica, Via Milanese, 300, 20099 Sesto San Giovanni (Milano), Italy

⁵ National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB), Eldor Lab, at the Innovation Accelerator, CNR, Via Piero Gobetti, 101, 40129 Bologna, Italy

⁶ Center for developmental biology and reprogramming, CEDEBIOR, Department of Biomedical Sciences, University of Sassari and National Institute of Biostructures and Biosystems, Viale San Pietro, 43/B, 07100 Sassari, Italy

⁷ Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, S.S 554 bivio per Sestu Km 4,500, 09042 Monserrato (Cagliari), Italy

⁸ Department of Biotechnology, University of Natural Resources and Life Sciences, Muthgasse, 18, A-1190 Vienna, Austria

⁹ Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse, 13, A-1200 Vienna, Austria

Send correspondence to: Professor Carlo Ventura, National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB), Eldor Lab, at the Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy. Mobile: 39 347 9206992, Tel: 39-051-2094104, Fax: 39-051-2094110, E-mail: carlo.ventura@unibo.it

Front. Biosci. (Schol Ed) 2019, 11(1), 89–104; https://doi.org/10.2741/S528

Published: 1 March 2019

(This article belongs to the Special Issue Unravelling stem cell fate: from genes and epigenetic toward cellular phenotypes)

Abstract

Human adult stem cells hold promise for regenerative medicine. They are usually expanded for multiple passages in vitro to increase cell yield prior to transplantation. Unfortunately, prolonged culture leads to cell senescence, a major drawback from successful outcomes in cell therapy approaches. Here, we show that an extract from early Zebrafish embryo (ZF1) counteracted senescence progression in human adipose-derived stem cells (hASCs) along multiple culture passages (from the 5^th to the 20^th). Exposure to ZF1 strongly reduced the expression of senescence marker beta-galactosidase. Both stemness (NANOG, OCT4, and MYC) and anti-senescence (BMI1, and telomerase reverse transcriptase - TERT) related genes were overexpressed at specific experimental points, without recruitment of the cyclin-dependent kinase Inhibitor 2A (CDKN2A, alias p16). Increased telomerase activity was associated with TERT overexpression. Both osteogenic and adipogenic abilities were enhanced. In conclusion, hASCs exposure to ZF1 is a feasible tool to counteract and reverse human stem cell senescence in long-term culturing conditions.