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Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions
BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are splendid cell sources for clinical application in the administration of numerous refractory and relapse diseases. Despite the preferable prospect of serum-free (SF) condition for cell product standardization and pathogenic contamination...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530421/ https://www.ncbi.nlm.nih.gov/pubmed/36195964 http://dx.doi.org/10.1186/s13287-022-03179-2 |
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author | Sun, Yunyan Wang, Ti-er Hu, Qianwen Zhang, Wenxia Zeng, Yun Lai, Xun Zhang, Leisheng Shi, Mingxia |
author_facet | Sun, Yunyan Wang, Ti-er Hu, Qianwen Zhang, Wenxia Zeng, Yun Lai, Xun Zhang, Leisheng Shi, Mingxia |
author_sort | Sun, Yunyan |
collection | PubMed |
description | BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are splendid cell sources for clinical application in the administration of numerous refractory and relapse diseases. Despite the preferable prospect of serum-free (SF) condition for cell product standardization and pathogenic contamination remission, yet the systematic and detailed impact upon hAMSCs at both cellular and transcriptomic levels is largely obscure. METHODS: For the purpose, we preconditioned hAMSCs under serum-containing (SC) and SF medium for 48 h and compared the biological signatures and biofunctions from the view of cell morphology, immunophenotypes, multi-lineage differentiation in vitro, cell vitality, cytokine expression, and immunosuppressive effect upon the subpopulations of T lymphocytes, together with the PI3K-AKT-mTOR signaling reactivation upon cell vitality. Meanwhile, we took advantage of RNA-SEQ and bioinformatic analyses to verify the gene expression profiling and genetic variation spectrum in the indicated hAMSCs. RESULTS: Compared with those maintained in SC medium, hAMSCs pretreated in SF conditions manifested conservation in cell morphology, immunophenotypes, adipogenic differentiation, and immunosuppressive effect upon the proliferation and activation of most of the T cell subpopulations, but with evaluated cytokine expression (e.g., TGF-β1, IDO1, NOS2) and declined osteogenic differentiation and cell proliferation as well as proapoptotic and apoptotic cells. The declined proliferation in the SF group was efficiently rescued by PI3K-AKT-mTOR signaling reactivation. Notably, hAMSCs cultured in SF and SC conditions revealed similarities in gene expression profiling and variations in genetic mutation at the transcriptome level. Instead, based on the differentially expressed genes and variable shear event analyses, we found those genes were mainly involved in DNA synthesis-, protein metabolism-, and cell vitality-associated biological processes and signaling pathways (e.g., P53, KRAS, PI3K-Akt-mTOR). CONCLUSIONS: Collectively, our data revealed the multifaceted cellular and molecular properties of hAMSCs under SC and SF conditions, which suggested the feasibility of serum-free culture for the preferable preparation of standardized cell products for hAMSC drug development and clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03179-2. |
format | Online Article Text |
id | pubmed-9530421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95304212022-10-04 Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions Sun, Yunyan Wang, Ti-er Hu, Qianwen Zhang, Wenxia Zeng, Yun Lai, Xun Zhang, Leisheng Shi, Mingxia Stem Cell Res Ther Research BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are splendid cell sources for clinical application in the administration of numerous refractory and relapse diseases. Despite the preferable prospect of serum-free (SF) condition for cell product standardization and pathogenic contamination remission, yet the systematic and detailed impact upon hAMSCs at both cellular and transcriptomic levels is largely obscure. METHODS: For the purpose, we preconditioned hAMSCs under serum-containing (SC) and SF medium for 48 h and compared the biological signatures and biofunctions from the view of cell morphology, immunophenotypes, multi-lineage differentiation in vitro, cell vitality, cytokine expression, and immunosuppressive effect upon the subpopulations of T lymphocytes, together with the PI3K-AKT-mTOR signaling reactivation upon cell vitality. Meanwhile, we took advantage of RNA-SEQ and bioinformatic analyses to verify the gene expression profiling and genetic variation spectrum in the indicated hAMSCs. RESULTS: Compared with those maintained in SC medium, hAMSCs pretreated in SF conditions manifested conservation in cell morphology, immunophenotypes, adipogenic differentiation, and immunosuppressive effect upon the proliferation and activation of most of the T cell subpopulations, but with evaluated cytokine expression (e.g., TGF-β1, IDO1, NOS2) and declined osteogenic differentiation and cell proliferation as well as proapoptotic and apoptotic cells. The declined proliferation in the SF group was efficiently rescued by PI3K-AKT-mTOR signaling reactivation. Notably, hAMSCs cultured in SF and SC conditions revealed similarities in gene expression profiling and variations in genetic mutation at the transcriptome level. Instead, based on the differentially expressed genes and variable shear event analyses, we found those genes were mainly involved in DNA synthesis-, protein metabolism-, and cell vitality-associated biological processes and signaling pathways (e.g., P53, KRAS, PI3K-Akt-mTOR). CONCLUSIONS: Collectively, our data revealed the multifaceted cellular and molecular properties of hAMSCs under SC and SF conditions, which suggested the feasibility of serum-free culture for the preferable preparation of standardized cell products for hAMSC drug development and clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03179-2. BioMed Central 2022-10-04 /pmc/articles/PMC9530421/ /pubmed/36195964 http://dx.doi.org/10.1186/s13287-022-03179-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sun, Yunyan Wang, Ti-er Hu, Qianwen Zhang, Wenxia Zeng, Yun Lai, Xun Zhang, Leisheng Shi, Mingxia Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title | Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title_full | Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title_fullStr | Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title_full_unstemmed | Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title_short | Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
title_sort | systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530421/ https://www.ncbi.nlm.nih.gov/pubmed/36195964 http://dx.doi.org/10.1186/s13287-022-03179-2 |
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