Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture
Mesenchymal stem cells (MSCs) play important roles in tissue regeneration, and multi-lineage differentiation and immunomodulation are two major characteristics of MSCs that are utilized in stem cell therapy. MSCs in vivo have a markedly different three-dimensional (3D) niche compared to the traditio...
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| Veröffentlicht in: | PloS one 2018-11, Vol.13 (11), p.e0206811-e0206811 |
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| creator | Li, Jing Chen, Tong Huang, Xiahe Zhao, Yunshan Wang, Bin Yin, Yanyun Cui, Yi Zhao, Yannan Zhang, Ruiping Wang, Xiujie Wang, Yingchun Dai, Jianwu |
| description | Mesenchymal stem cells (MSCs) play important roles in tissue regeneration, and multi-lineage differentiation and immunomodulation are two major characteristics of MSCs that are utilized in stem cell therapy. MSCs in vivo have a markedly different three-dimensional (3D) niche compared to the traditional two-dimensional (2D) culture in vitro. A 3D scaffold is predicted to provide an artificial 3D environment similar to the in vivo environment. Significant changes in MSC differentiation are shown to be occurred when under 3D culture. However, the immunomodulatory characteristics of MSCs under 3D culture remain unknown. In this study, 3D culture systems were constructed using different substrates to evaluate the common immunomodulatory characteristics of MSCs. Compared to the MSCs under 2D culture, the MSCs under 3D culture, which had higher stemness and maintained cell phenotype, showed altered immunophenotypic pattern. Gene expression profile analysis at mRNA and protein level detected by gene chip and protein chip, respectively, further revealed the difference between 3D cultured MSCs and 2D cultured MSCs, which was mainly concentrated in the immunoregulation related aspects. Moreover, the immunoregulatory role of 3D culture was confirmed by our immunosuppressive experiments. These findings demonstrated that the immunomodulatory capacities of MSCs were enhanced by the 3D geometry of substrates. |
| doi_str_mv | 10.1371/journal.pone.0206811 |
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MSCs in vivo have a markedly different three-dimensional (3D) niche compared to the traditional two-dimensional (2D) culture in vitro. A 3D scaffold is predicted to provide an artificial 3D environment similar to the in vivo environment. Significant changes in MSC differentiation are shown to be occurred when under 3D culture. However, the immunomodulatory characteristics of MSCs under 3D culture remain unknown. In this study, 3D culture systems were constructed using different substrates to evaluate the common immunomodulatory characteristics of MSCs. Compared to the MSCs under 2D culture, the MSCs under 3D culture, which had higher stemness and maintained cell phenotype, showed altered immunophenotypic pattern. Gene expression profile analysis at mRNA and protein level detected by gene chip and protein chip, respectively, further revealed the difference between 3D cultured MSCs and 2D cultured MSCs, which was mainly concentrated in the immunoregulation related aspects. Moreover, the immunoregulatory role of 3D culture was confirmed by our immunosuppressive experiments. These findings demonstrated that the immunomodulatory capacities of MSCs were enhanced by the 3D geometry of substrates.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0206811</identifier><identifier>PMID: 30408051</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Arthritis ; Biology and Life Sciences ; Biomedical materials ; Bone marrow ; Cell adhesion & migration ; Cell culture ; Cell Culture Techniques - methods ; Cell Differentiation - immunology ; Cell Proliferation ; Developmental biology ; Differentiation ; Gene expression ; Genomics ; Growth factors ; Guided Tissue Regeneration ; Hospitals ; Humans ; Immunomodulation ; Immunoregulation ; Immunosuppression ; Immunosuppressive agents ; Laboratories ; Medicine and Health Sciences ; Mesenchymal stem cells ; Mesenchymal Stem Cells - immunology ; Mesenchyme ; Morphology ; Pattern analysis ; Phenotypes ; Proteins ; Proteomics ; Regeneration ; Research and Analysis Methods ; Scanning electron microscopy ; Stem cells ; Substrates ; Tissue engineering ; Tissue Scaffolds ; Topography ; Umbilical cord</subject><ispartof>PloS one, 2018-11, Vol.13 (11), p.e0206811-e0206811</ispartof><rights>2018 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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MSCs in vivo have a markedly different three-dimensional (3D) niche compared to the traditional two-dimensional (2D) culture in vitro. A 3D scaffold is predicted to provide an artificial 3D environment similar to the in vivo environment. Significant changes in MSC differentiation are shown to be occurred when under 3D culture. However, the immunomodulatory characteristics of MSCs under 3D culture remain unknown. In this study, 3D culture systems were constructed using different substrates to evaluate the common immunomodulatory characteristics of MSCs. Compared to the MSCs under 2D culture, the MSCs under 3D culture, which had higher stemness and maintained cell phenotype, showed altered immunophenotypic pattern. Gene expression profile analysis at mRNA and protein level detected by gene chip and protein chip, respectively, further revealed the difference between 3D cultured MSCs and 2D cultured MSCs, which was mainly concentrated in the immunoregulation related aspects. 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These findings demonstrated that the immunomodulatory capacities of MSCs were enhanced by the 3D geometry of substrates.</description><subject>Arthritis</subject><subject>Biology and Life Sciences</subject><subject>Biomedical materials</subject><subject>Bone marrow</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Proliferation</subject><subject>Developmental biology</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Growth factors</subject><subject>Guided Tissue Regeneration</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Immunosuppression</subject><subject>Immunosuppressive agents</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - immunology</subject><subject>Mesenchyme</subject><subject>Morphology</subject><subject>Pattern analysis</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Regeneration</subject><subject>Research and Analysis Methods</subject><subject>Scanning electron microscopy</subject><subject>Stem cells</subject><subject>Substrates</subject><subject>Tissue engineering</subject><subject>Tissue Scaffolds</subject><subject>Topography</subject><subject>Umbilical cord</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUjRCIlsIfIIjEhk0GP5JMvEFCFY9KlVgAa-vGvu545MdgO0jz9ySdtGoRG9uyzz33nOtTVa8p2VC-pR_2cUoB3OYQA24II_1A6ZPqnArOmp4R_vTB-ax6kfOekI4Pff-8OuOkJQPp6Hnlf0xjLgkKNjZoPOC8hFJb76cQfdSTgxLTsVY7SKAKJpuLVbmOpvaYMajd0YOrc0FfK3Qu1zbUZZcQG209hmzjLLJWkytTwpfVMwMu46t1v6h-ffn88_Jbc_3969Xlp-tGdawvzah5C8TQbtujoMCoAS3UIEZugLY9ci3QbFmvWlBaCzpsjRi7wRhDcOQd4xfV2xPvwcUs10llySinjBHRkRlxdULoCHt5SNZDOsoIVt5exHQjIc1OHUqitFEtEsU6aAUdYWCCMGCzHDW2fOn2ce02jR61mgeYwD0iffwS7E7exD-yZ2z-BzoTvF8JUvw9YS7S27xMEwLG6VY3Yx0TfIG--wf6f3ftCaVSzDmhuRdDiVzSc1cll_TINT1z2ZuHRu6L7uLC_wKDNMbq</recordid><startdate>20181108</startdate><enddate>20181108</enddate><creator>Li, Jing</creator><creator>Chen, Tong</creator><creator>Huang, Xiahe</creator><creator>Zhao, Yunshan</creator><creator>Wang, Bin</creator><creator>Yin, Yanyun</creator><creator>Cui, Yi</creator><creator>Zhao, Yannan</creator><creator>Zhang, Ruiping</creator><creator>Wang, Xiujie</creator><creator>Wang, Yingchun</creator><creator>Dai, Jianwu</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8914-4005</orcidid></search><sort><creationdate>20181108</creationdate><title>Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture</title><author>Li, Jing ; Chen, Tong ; Huang, Xiahe ; Zhao, Yunshan ; Wang, Bin ; Yin, Yanyun ; Cui, Yi ; Zhao, Yannan ; Zhang, Ruiping ; Wang, Xiujie ; Wang, Yingchun ; Dai, Jianwu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-bd34a0f1576e91a21fad9c89b3fa146e3d9ef726c4acdd9187f9b58fff0eb3523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Arthritis</topic><topic>Biology and Life Sciences</topic><topic>Biomedical materials</topic><topic>Bone marrow</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell Culture Techniques - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jing</au><au>Chen, Tong</au><au>Huang, Xiahe</au><au>Zhao, Yunshan</au><au>Wang, Bin</au><au>Yin, Yanyun</au><au>Cui, Yi</au><au>Zhao, Yannan</au><au>Zhang, Ruiping</au><au>Wang, Xiujie</au><au>Wang, Yingchun</au><au>Dai, Jianwu</au><au>Gronthos, Stan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-11-08</date><risdate>2018</risdate><volume>13</volume><issue>11</issue><spage>e0206811</spage><epage>e0206811</epage><pages>e0206811-e0206811</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mesenchymal stem cells (MSCs) play important roles in tissue regeneration, and multi-lineage differentiation and immunomodulation are two major characteristics of MSCs that are utilized in stem cell therapy. MSCs in vivo have a markedly different three-dimensional (3D) niche compared to the traditional two-dimensional (2D) culture in vitro. A 3D scaffold is predicted to provide an artificial 3D environment similar to the in vivo environment. Significant changes in MSC differentiation are shown to be occurred when under 3D culture. However, the immunomodulatory characteristics of MSCs under 3D culture remain unknown. In this study, 3D culture systems were constructed using different substrates to evaluate the common immunomodulatory characteristics of MSCs. Compared to the MSCs under 2D culture, the MSCs under 3D culture, which had higher stemness and maintained cell phenotype, showed altered immunophenotypic pattern. Gene expression profile analysis at mRNA and protein level detected by gene chip and protein chip, respectively, further revealed the difference between 3D cultured MSCs and 2D cultured MSCs, which was mainly concentrated in the immunoregulation related aspects. Moreover, the immunoregulatory role of 3D culture was confirmed by our immunosuppressive experiments. These findings demonstrated that the immunomodulatory capacities of MSCs were enhanced by the 3D geometry of substrates.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30408051</pmid><doi>10.1371/journal.pone.0206811</doi><orcidid>https://orcid.org/0000-0002-8914-4005</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Arthritis Biology and Life Sciences Biomedical materials Bone marrow Cell adhesion & migration Cell culture Cell Culture Techniques - methods Cell Differentiation - immunology Cell Proliferation Developmental biology Differentiation Gene expression Genomics Growth factors Guided Tissue Regeneration Hospitals Humans Immunomodulation Immunoregulation Immunosuppression Immunosuppressive agents Laboratories Medicine and Health Sciences Mesenchymal stem cells Mesenchymal Stem Cells - immunology Mesenchyme Morphology Pattern analysis Phenotypes Proteins Proteomics Regeneration Research and Analysis Methods Scanning electron microscopy Stem cells Substrates Tissue engineering Tissue Scaffolds Topography Umbilical cord |
| title | Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture |
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