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Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation
Variability among donors, non-standardized methods for isolation, and characterization contribute to mesenchymal stem/stromal cell (MSC) heterogeneity. Induced pluripotent stem cell (iPSCs)-derived MSCs would circumvent many of current issues and enable large-scale production of standardized cellula...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426992/ https://www.ncbi.nlm.nih.gov/pubmed/30894508 http://dx.doi.org/10.1038/s41419-019-1498-0 |
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author | Devito, Liani Klontzas, Michail E. Cvoro, Aleksandra Galleu, Antonio Simon, Marisa Hobbs, Carl Dazzi, Francesco Mantalaris, Athanasios Khalaf, Yacoub Ilic, Dusko |
author_facet | Devito, Liani Klontzas, Michail E. Cvoro, Aleksandra Galleu, Antonio Simon, Marisa Hobbs, Carl Dazzi, Francesco Mantalaris, Athanasios Khalaf, Yacoub Ilic, Dusko |
author_sort | Devito, Liani |
collection | PubMed |
description | Variability among donors, non-standardized methods for isolation, and characterization contribute to mesenchymal stem/stromal cell (MSC) heterogeneity. Induced pluripotent stem cell (iPSCs)-derived MSCs would circumvent many of current issues and enable large-scale production of standardized cellular therapy. To explore differences between native MSCs (nMSCs) and iPSC-derived MSCs (iMSCs), we developed isogeneic lines from Wharton’s jelly (WJ) from the umbilical cords of two donors (#12 and #13) under xeno-free conditions. Next, we reprogrammed them into iPSCs (iPSC12 and iPSC13) and subsequently differentiated them back into iMSCs (iMSC12 and iMSC13) using two different protocols, which we named ARG and TEX. We assessed their differentiation capability, transcriptome, immunomodulatory potential, and interferon-γ (IFNG)-induced changes in metabolome. Our data demonstrated that although both differentiation protocols yield iMSCs similar to their parental nMSCs, there are substantial differences. The ARG protocol resulted in iMSCs with a strong immunomodulatory potential and lower plasticity and proliferation rate, whereas the TEX protocol raised iMSCs with a higher proliferation rate, better differentiation potential, though weak immunomodulatory response. Our data suggest that, following a careful selection and screening of donors, nMSCs from umbilical’s cord WJ can be easily reprogrammed into iPSCs, providing an unlimited source of material for differentiation into iMSCs. However, the differentiation protocol should be chosen depending on their clinical use. |
format | Online Article Text |
id | pubmed-6426992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64269922019-03-21 Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation Devito, Liani Klontzas, Michail E. Cvoro, Aleksandra Galleu, Antonio Simon, Marisa Hobbs, Carl Dazzi, Francesco Mantalaris, Athanasios Khalaf, Yacoub Ilic, Dusko Cell Death Dis Article Variability among donors, non-standardized methods for isolation, and characterization contribute to mesenchymal stem/stromal cell (MSC) heterogeneity. Induced pluripotent stem cell (iPSCs)-derived MSCs would circumvent many of current issues and enable large-scale production of standardized cellular therapy. To explore differences between native MSCs (nMSCs) and iPSC-derived MSCs (iMSCs), we developed isogeneic lines from Wharton’s jelly (WJ) from the umbilical cords of two donors (#12 and #13) under xeno-free conditions. Next, we reprogrammed them into iPSCs (iPSC12 and iPSC13) and subsequently differentiated them back into iMSCs (iMSC12 and iMSC13) using two different protocols, which we named ARG and TEX. We assessed their differentiation capability, transcriptome, immunomodulatory potential, and interferon-γ (IFNG)-induced changes in metabolome. Our data demonstrated that although both differentiation protocols yield iMSCs similar to their parental nMSCs, there are substantial differences. The ARG protocol resulted in iMSCs with a strong immunomodulatory potential and lower plasticity and proliferation rate, whereas the TEX protocol raised iMSCs with a higher proliferation rate, better differentiation potential, though weak immunomodulatory response. Our data suggest that, following a careful selection and screening of donors, nMSCs from umbilical’s cord WJ can be easily reprogrammed into iPSCs, providing an unlimited source of material for differentiation into iMSCs. However, the differentiation protocol should be chosen depending on their clinical use. Nature Publishing Group UK 2019-03-20 /pmc/articles/PMC6426992/ /pubmed/30894508 http://dx.doi.org/10.1038/s41419-019-1498-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Devito, Liani Klontzas, Michail E. Cvoro, Aleksandra Galleu, Antonio Simon, Marisa Hobbs, Carl Dazzi, Francesco Mantalaris, Athanasios Khalaf, Yacoub Ilic, Dusko Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title | Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title_full | Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title_fullStr | Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title_full_unstemmed | Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title_short | Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation |
title_sort | comparison of human isogeneic wharton’s jelly mscs and ipsc-derived mscs reveals differentiation-dependent metabolic responses to ifng stimulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426992/ https://www.ncbi.nlm.nih.gov/pubmed/30894508 http://dx.doi.org/10.1038/s41419-019-1498-0 |
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