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Int J Mol Sci. 2019 May 29;20(11). pii: E2646. doi: 10.3390/ijms20112646.

Early Developmental Zebrafish Embryo Extract to Modulate Senescence in Multisource Human Mesenchymal Stem Cells.

Author information

1
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. federica.facchin2@unibo.it.
2
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. federica.facchin2@unibo.it.
3
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. francesco.alviano@unibo.it.
4
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. silvia.canaider@unibo.it.
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. silvia.canaider@unibo.it.
6
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. eva.bianconi2@unibo.it.
7
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. eva.bianconi2@unibo.it.
8
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. martina.rossi12@unibo.it.
9
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. laura.bonsi@unibo.it.
10
Department for Life Quality Studies (QuVi), University of Bologna, Corso D'Augusto 237, 47921 Rimini, Italy. r.casadei@unibo.it.
11
Scientific Institute of Research and Care Multimedica, Via Milanese 300, 20099 Sesto San Giovanni (Milano), Italy. biava@tiscali.it.
12
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. carlo.ventura@unibo.it.
13
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. carlo.ventura@unibo.it.

Abstract

Stem cells undergo senescence both in vivo, contributing to the progressive decline in self-healing mechanisms, and in vitro during prolonged expansion. Here, we show that an early developmental zebrafish embryo extract (ZF1) could act as a modulator of senescence in human mesenchymal stem cells (hMSCs) isolated from both adult tissues, including adipose tissue (hASCs), bone marrow (hBM-MSCs), dental pulp (hDP-MSCs), and a perinatal tissue such as the Wharton's Jelly (hWJ-MSCs). In all the investigated hMSCs, ZF1 decreased senescence-associated β-galactosidase (SA β-gal) activity and enhanced the transcription of TERT, encoding the catalytic telomerase core. In addition, it was associated, only in hASCs, with a transcriptional induction of BMI1, a pleiotropic repressor of senescence. In hBM-MSCs, hDP-MSCs, and hWJ-MSCs, TERT over-expression was concomitant with a down-regulation of two repressors of TERT, TP53 (p53), and CDKN1A (p21). Furthermore, ZF1 increased the natural ability of hASCs to perform adipogenesis. These results indicate the chance of using ZF1 to modulate stem cell senescence in a source-related manner, to be potentially used as a tool to affect stem cell senescence in vitro. In addition, its anti-senescence action could also set the basis for future in vivo approaches promoting tissue rejuvenation bypassing stem cell transplantation.

KEYWORDS:

BMI1; TERT; adipogenesis; p16; p21; p53; senescence; senescence-associated β-galactosidase activity; stem cells; zebrafish embryo extract

PMID:
31146388
DOI:
10.3390/ijms20112646
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