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Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/st...

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Autores principales: Novoseletskaya, Ekaterina, Grigorieva, Olga, Nimiritsky, Peter, Basalova, Nataliya, Eremichev, Roman, Milovskaya, Irina, Kulebyakin, Konstantin, Kulebyakina, Maria, Rodionov, Sergei, Omelyanenko, Nikolai, Efimenko, Anastasia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536557/
https://www.ncbi.nlm.nih.gov/pubmed/33072743
http://dx.doi.org/10.3389/fcell.2020.555378
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author Novoseletskaya, Ekaterina
Grigorieva, Olga
Nimiritsky, Peter
Basalova, Nataliya
Eremichev, Roman
Milovskaya, Irina
Kulebyakin, Konstantin
Kulebyakina, Maria
Rodionov, Sergei
Omelyanenko, Nikolai
Efimenko, Anastasia
author_facet Novoseletskaya, Ekaterina
Grigorieva, Olga
Nimiritsky, Peter
Basalova, Nataliya
Eremichev, Roman
Milovskaya, Irina
Kulebyakin, Konstantin
Kulebyakina, Maria
Rodionov, Sergei
Omelyanenko, Nikolai
Efimenko, Anastasia
author_sort Novoseletskaya, Ekaterina
collection PubMed
description Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.
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spelling pubmed-75365572020-10-16 Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli Novoseletskaya, Ekaterina Grigorieva, Olga Nimiritsky, Peter Basalova, Nataliya Eremichev, Roman Milovskaya, Irina Kulebyakin, Konstantin Kulebyakina, Maria Rodionov, Sergei Omelyanenko, Nikolai Efimenko, Anastasia Front Cell Dev Biol Cell and Developmental Biology Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine. Frontiers Media S.A. 2020-09-22 /pmc/articles/PMC7536557/ /pubmed/33072743 http://dx.doi.org/10.3389/fcell.2020.555378 Text en Copyright © 2020 Novoseletskaya, Grigorieva, Nimiritsky, Basalova, Eremichev, Milovskaya, Kulebyakin, Kulebyakina, Rodionov, Omelyanenko and Efimenko. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Novoseletskaya, Ekaterina
Grigorieva, Olga
Nimiritsky, Peter
Basalova, Nataliya
Eremichev, Roman
Milovskaya, Irina
Kulebyakin, Konstantin
Kulebyakina, Maria
Rodionov, Sergei
Omelyanenko, Nikolai
Efimenko, Anastasia
Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title_full Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title_fullStr Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title_full_unstemmed Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title_short Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli
title_sort mesenchymal stromal cell-produced components of extracellular matrix potentiate multipotent stem cell response to differentiation stimuli
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536557/
https://www.ncbi.nlm.nih.gov/pubmed/33072743
http://dx.doi.org/10.3389/fcell.2020.555378
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