Antioxidant, Pro-Survival and Pro-Regenerative Effects of Conditioned Medium from Wharton’s Jelly Mesenchymal Stem Cells on Developing Zebrafish Embryos

Antioxidant, Pro-Survival and Pro-Regenerative Effects of Conditioned Medium from Wharton’s Jelly Mesenchymal Stem Cells on Developing Zebrafish Embryos

Conditioned media harvested from stem cell culturing have the potential to be innovative therapeutic tools against various diseases, due to their high content of growth, trophic and protective factors. The evaluation in vivo of the effects and biosafety of these products is essential, and zebrafish...

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Published in:International journal of molecular sciences Vol. 24; no. 17; p. 13191
Main Authors: Reina, Chiara, Cardella, Clara, Lo Pinto, Margot, Pucci, Gaia, Acuto, Santina, Maggio, Aurelio, Cavalieri, Vincenzo
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-09-2023
MDPI
Subjects:
antioxidant
Antioxidants
Brain-derived neurotrophic factor
conditioned medium
Epigenetics
Gene expression
Health aspects
histone post-translational modifications
Homeostasis
Morphology
regeneration
Stem cells
Umbilical cord
Wharton’s jelly mesenchymal stem cells
Zebrafish
France
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Summary:Conditioned media harvested from stem cell culturing have the potential to be innovative therapeutic tools against various diseases, due to their high content of growth, trophic and protective factors. The evaluation in vivo of the effects and biosafety of these products is essential, and zebrafish provides an ideal platform for high-throughput toxicological analysis, concurrently allowing the minimization of the use of mammalian models without losing reliability. In this study, we assessed the biological effects elicited by the exposure of zebrafish embryos to a conditioned medium derived from Wharton’s jelly mesenchymal stem cells. By a multiparametric investigation combining molecular, embryological, behavioural and in vivo imaging techniques, we found that exposure to a conditioned medium at a non-toxic/non-lethal dosage triggers antioxidant, anti-apoptotic and pro-regenerative effects, by upregulation of a set of genes involved in antioxidant defence (nrf2, brg1, sirt1, sirt6, foxO3a, sod2 and cat), glycolysis (ldha) and cell survival (bcl2l1, mcl1a and bim), coupled to downregulation of pro-apoptotic markers (baxa, caspase-3a and caspase-8). To our knowledge, this is the first study comprehensively addressing the effects of a conditioned medium on a whole organism from a developmental, molecular and behavioural perspective, and we are fairly confident that it will pave the way for future therapeutic application.
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Current address: Candiolo Cancer Institute FPO IRCCS, Strada Provinciale 142, 10060 Torino, Italy.
Current address: Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Cefalù Secondary Site, C/da Pietrapollastra-Pisciotto, 90015 Cefalù, Italy.
These authors contributed equally to the work.
Current address: Cancer Imaging Unit, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241713191