PUBLICATION
Early Developmental Zebrafish Embryo Extract to Modulate Senescence in Multisource Human Mesenchymal Stem Cells
- Authors
- Facchin, F., Alviano, F., Canaider, S., Bianconi, E., Rossi, M., Bonsi, L., Casadei, R., Biava, P.M., Ventura, C.
- ID
- ZDB-PUB-190601-13
- Date
- 2019
- Source
- International Journal of Molecular Sciences 20(11): (Journal)
- Registered Authors
- Casadei, Raffaella
- Keywords
- BMI1, TERT, adipogenesis, p16, p21, p53, senescence, senescence-associated β-galactosidase activity, stem cells, zebrafish embryo extract
- MeSH Terms
-
- Animals
- Cells, Cultured
- Cellular Senescence*
- Cyclin-Dependent Kinase Inhibitor p21/genetics
- Cyclin-Dependent Kinase Inhibitor p21/metabolism
- Embryo, Nonmammalian/chemistry*
- Humans
- Mesenchymal Stem Cells/cytology
- Mesenchymal Stem Cells/drug effects*
- Mesenchymal Stem Cells/metabolism
- Polycomb Repressive Complex 1/genetics
- Polycomb Repressive Complex 1/metabolism
- Telomerase/genetics
- Telomerase/metabolism
- Tissue Extracts/pharmacology*
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- PubMed
- 31146388 Full text @ Int. J. Mol. Sci.
Citation
Facchin, F., Alviano, F., Canaider, S., Bianconi, E., Rossi, M., Bonsi, L., Casadei, R., Biava, P.M., Ventura, C. (2019) Early Developmental Zebrafish Embryo Extract to Modulate Senescence in Multisource Human Mesenchymal Stem Cells. International Journal of Molecular Sciences. 20(11).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping