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Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)

BACKGROUND: Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of...

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Autores principales: Zavala, Gabriela, Prieto, Catalina P., Villanueva, Andrea A., Palma, Verónica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622478/
https://www.ncbi.nlm.nih.gov/pubmed/28962669
http://dx.doi.org/10.1186/s13287-017-0653-8
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author Zavala, Gabriela
Prieto, Catalina P.
Villanueva, Andrea A.
Palma, Verónica
author_facet Zavala, Gabriela
Prieto, Catalina P.
Villanueva, Andrea A.
Palma, Verónica
author_sort Zavala, Gabriela
collection PubMed
description BACKGROUND: Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of these specific factors are still mostly unknown. Emerging evidence suggests that Sonic hedgehog (SHH) plays a central role in angiogenesis and tissue maintenance. However, its contribution to the angiogenic potential of MSC has not been fully addressed. The aim of this work was to characterize the expression of the SHH pathway components in WJ-MSC primary cultures and to evaluate their angiogenic responsiveness to SHH signaling. METHODS: Primary cell cultures obtained from human umbilical cords were treated with pharmacological modulators of the SHH pathway. We evaluated the modulation of diverse trophic factors in cell lysates, conditioned medium, and functional in vitro assays. In addition, we determined the angiogenic potential of the SHH pathway in the chicken chorioallantoic membrane, an in vivo model. RESULTS: Our results show that WJ-MSC express components of the canonical SHH pathway and are activated by its signaling. In fact, we provide evidence of basal autocrine/paracrine SHH signaling in WJ-MSC. SHH pathway stimulation promotes the secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase -9, and urokinase-type plasminogen activator, enhancing the pro-angiogenic capabilities of WJ-MSC both in vitro and in vivo. CONCLUSION: WJ-MSC are a cell population responsive to SHH pathway stimulation. Basal SHH signaling is in part responsible for the angiogenic inductive properties of WJ-MSC. Overall, exogenous activation of the SHH pathway enhances the angiogenic properties of WJ-MSC, making this cell population an ideal target for treating tissue injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0653-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-56224782017-10-11 Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC) Zavala, Gabriela Prieto, Catalina P. Villanueva, Andrea A. Palma, Verónica Stem Cell Res Ther Research BACKGROUND: Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of these specific factors are still mostly unknown. Emerging evidence suggests that Sonic hedgehog (SHH) plays a central role in angiogenesis and tissue maintenance. However, its contribution to the angiogenic potential of MSC has not been fully addressed. The aim of this work was to characterize the expression of the SHH pathway components in WJ-MSC primary cultures and to evaluate their angiogenic responsiveness to SHH signaling. METHODS: Primary cell cultures obtained from human umbilical cords were treated with pharmacological modulators of the SHH pathway. We evaluated the modulation of diverse trophic factors in cell lysates, conditioned medium, and functional in vitro assays. In addition, we determined the angiogenic potential of the SHH pathway in the chicken chorioallantoic membrane, an in vivo model. RESULTS: Our results show that WJ-MSC express components of the canonical SHH pathway and are activated by its signaling. In fact, we provide evidence of basal autocrine/paracrine SHH signaling in WJ-MSC. SHH pathway stimulation promotes the secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase -9, and urokinase-type plasminogen activator, enhancing the pro-angiogenic capabilities of WJ-MSC both in vitro and in vivo. CONCLUSION: WJ-MSC are a cell population responsive to SHH pathway stimulation. Basal SHH signaling is in part responsible for the angiogenic inductive properties of WJ-MSC. Overall, exogenous activation of the SHH pathway enhances the angiogenic properties of WJ-MSC, making this cell population an ideal target for treating tissue injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0653-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-29 /pmc/articles/PMC5622478/ /pubmed/28962669 http://dx.doi.org/10.1186/s13287-017-0653-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zavala, Gabriela
Prieto, Catalina P.
Villanueva, Andrea A.
Palma, Verónica
Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title_full Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title_fullStr Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title_full_unstemmed Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title_short Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC)
title_sort sonic hedgehog (shh) signaling improves the angiogenic potential of wharton’s jelly-derived mesenchymal stem cells (wj-msc)
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622478/
https://www.ncbi.nlm.nih.gov/pubmed/28962669
http://dx.doi.org/10.1186/s13287-017-0653-8
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