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Front Biosci (Schol Ed). 2019 Mar 1;11:89-104.

Zebrafish embryo extract counteracts human stem cell senescence.

Author information

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
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy, carlo.ventura@ unibo.it.

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 5th to the 20th). 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, ali-as p16). Increased telomerase activity was associatt-ed 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.

PMID:
30844738

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