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3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells
Mechanical stimuli from the extracellular environment affect cell morphology and functionality. Recently, we reported that mesenchymal stem cells (MSCs) grown in a custom-made 3D microscaffold, the Nichoid, are able to express higher levels of stemness markers. In fact, the Nichoid is an interesting...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AIP Publishing LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491463/ https://www.ncbi.nlm.nih.gov/pubmed/37692376 http://dx.doi.org/10.1063/5.0153215 |
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author | Donnaloja, Francesca Raimondi, Manuela Teresa Messa, Letizia Barzaghini, Bianca Carnevali, Federica Colombo, Emanuele Mazza, Davide Martinelli, Chiara Boeri, Lucia Rey, Federica Cereda, Cristina Osellame, Roberto Cerullo, Giulio Carelli, Stephana Soncini, Monica Jacchetti, Emanuela |
author_facet | Donnaloja, Francesca Raimondi, Manuela Teresa Messa, Letizia Barzaghini, Bianca Carnevali, Federica Colombo, Emanuele Mazza, Davide Martinelli, Chiara Boeri, Lucia Rey, Federica Cereda, Cristina Osellame, Roberto Cerullo, Giulio Carelli, Stephana Soncini, Monica Jacchetti, Emanuela |
author_sort | Donnaloja, Francesca |
collection | PubMed |
description | Mechanical stimuli from the extracellular environment affect cell morphology and functionality. Recently, we reported that mesenchymal stem cells (MSCs) grown in a custom-made 3D microscaffold, the Nichoid, are able to express higher levels of stemness markers. In fact, the Nichoid is an interesting device for autologous MSC expansion in clinical translation and would appear to regulate gene activity by altering intracellular force transmission. To corroborate this hypothesis, we investigated mechanotransduction-related nuclear mechanisms, and we also treated spread cells with a drug that destroys the actin cytoskeleton. We observed a roundish nuclear shape in MSCs cultured in the Nichoid and correlated the nuclear curvature with the import of transcription factors. We observed a more homogeneous euchromatin distribution in cells cultured in the Nichoid with respect to the Flat sample, corresponding to a standard glass coverslip. These results suggest a different gene regulation, which we confirmed by an RNA-seq analysis that revealed the dysregulation of 1843 genes. We also observed a low structured lamina mesh, which, according to the implemented molecular dynamic simulations, indicates reduced damping activity, thus supporting the hypothesis of low intracellular force transmission. Also, our investigations regarding lamin expression and spatial organization support the hypothesis that the gene dysregulation induced by the Nichoid is mainly related to a reduction in force transmission. In conclusion, our findings revealing the Nichoid's effects on MSC behavior is a step forward in the control of stem cells via mechanical manipulation, thus paving the way to new strategies for MSC translation to clinical applications. |
format | Online Article Text |
id | pubmed-10491463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-104914632023-09-09 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells Donnaloja, Francesca Raimondi, Manuela Teresa Messa, Letizia Barzaghini, Bianca Carnevali, Federica Colombo, Emanuele Mazza, Davide Martinelli, Chiara Boeri, Lucia Rey, Federica Cereda, Cristina Osellame, Roberto Cerullo, Giulio Carelli, Stephana Soncini, Monica Jacchetti, Emanuela APL Bioeng Articles Mechanical stimuli from the extracellular environment affect cell morphology and functionality. Recently, we reported that mesenchymal stem cells (MSCs) grown in a custom-made 3D microscaffold, the Nichoid, are able to express higher levels of stemness markers. In fact, the Nichoid is an interesting device for autologous MSC expansion in clinical translation and would appear to regulate gene activity by altering intracellular force transmission. To corroborate this hypothesis, we investigated mechanotransduction-related nuclear mechanisms, and we also treated spread cells with a drug that destroys the actin cytoskeleton. We observed a roundish nuclear shape in MSCs cultured in the Nichoid and correlated the nuclear curvature with the import of transcription factors. We observed a more homogeneous euchromatin distribution in cells cultured in the Nichoid with respect to the Flat sample, corresponding to a standard glass coverslip. These results suggest a different gene regulation, which we confirmed by an RNA-seq analysis that revealed the dysregulation of 1843 genes. We also observed a low structured lamina mesh, which, according to the implemented molecular dynamic simulations, indicates reduced damping activity, thus supporting the hypothesis of low intracellular force transmission. Also, our investigations regarding lamin expression and spatial organization support the hypothesis that the gene dysregulation induced by the Nichoid is mainly related to a reduction in force transmission. In conclusion, our findings revealing the Nichoid's effects on MSC behavior is a step forward in the control of stem cells via mechanical manipulation, thus paving the way to new strategies for MSC translation to clinical applications. AIP Publishing LLC 2023-09-07 /pmc/articles/PMC10491463/ /pubmed/37692376 http://dx.doi.org/10.1063/5.0153215 Text en © 2023 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Articles Donnaloja, Francesca Raimondi, Manuela Teresa Messa, Letizia Barzaghini, Bianca Carnevali, Federica Colombo, Emanuele Mazza, Davide Martinelli, Chiara Boeri, Lucia Rey, Federica Cereda, Cristina Osellame, Roberto Cerullo, Giulio Carelli, Stephana Soncini, Monica Jacchetti, Emanuela 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title | 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title_full | 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title_fullStr | 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title_full_unstemmed | 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title_short | 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
title_sort | 3d photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491463/ https://www.ncbi.nlm.nih.gov/pubmed/37692376 http://dx.doi.org/10.1063/5.0153215 |
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