Adipose-Derived Mesenchymal Stem Cell (MSC) Immortalization by Modulation of hTERT and TP53 Expression Levels
Mesenchymal stem cells (MSCs) are pivotal players in tissue repair and hold great promise as cell therapeutic agents for regenerative medicine. Additionally, they play a significant role in the development of various human diseases. Studies on MSC biology have encountered a limiting property of thes...
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Veröffentlicht in: | Journal of personalized medicine 2023-11, Vol.13 (11), p.1621 |
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container_title | Journal of personalized medicine |
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creator | Rakhmatullina, Aigul Mingaleeva, Rimma Gafurbaeva, Dina Glazunova, Olesya Sagdeeva, Aisylu Bulatov, Emil Rizvanov, Albert Miftakhova, Regina |
description | Mesenchymal stem cells (MSCs) are pivotal players in tissue repair and hold great promise as cell therapeutic agents for regenerative medicine. Additionally, they play a significant role in the development of various human diseases. Studies on MSC biology have encountered a limiting property of these cells, which includes a low number of passages and a decrease in differentiation potential during in vitro culture. Although common methods of immortalization through gene manipulations of cells are well established, the resulting MSCs vary in differentiation potential compared to primary cells and eventually undergo senescence. This study aimed to immortalize primary adipose-derived MSCs by overexpressing human telomerase reverse transcriptase (hTERT) gene combined with a knockdown of TP53. The research demonstrated that immortalized MSCs maintained a stable level of differentiation into osteogenic and chondrogenic lineages during 30 passages, while also exhibiting an increase in cell proliferation rate and differentiation potential towards the adipogenic lineage. Long-term culture of immortalized cells did not alter cell morphology and self-renewal potential. Consequently, a genetically stable line of immortalized adipose-derived MSCs (iMSCs) was established. |
doi_str_mv | 10.3390/jpm13111621 |
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Additionally, they play a significant role in the development of various human diseases. Studies on MSC biology have encountered a limiting property of these cells, which includes a low number of passages and a decrease in differentiation potential during in vitro culture. Although common methods of immortalization through gene manipulations of cells are well established, the resulting MSCs vary in differentiation potential compared to primary cells and eventually undergo senescence. This study aimed to immortalize primary adipose-derived MSCs by overexpressing human telomerase reverse transcriptase (hTERT) gene combined with a knockdown of TP53. The research demonstrated that immortalized MSCs maintained a stable level of differentiation into osteogenic and chondrogenic lineages during 30 passages, while also exhibiting an increase in cell proliferation rate and differentiation potential towards the adipogenic lineage. Long-term culture of immortalized cells did not alter cell morphology and self-renewal potential. Consequently, a genetically stable line of immortalized adipose-derived MSCs (iMSCs) was established.</description><identifier>ISSN: 2075-4426</identifier><identifier>EISSN: 2075-4426</identifier><identifier>DOI: 10.3390/jpm13111621</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antigens ; Bone marrow ; Cancer therapies ; Cell culture ; Cell cycle ; Cell differentiation ; Cell division ; Cell growth ; Cell proliferation ; Cell self-renewal ; Cytology ; Fibroblasts ; Genes ; Genetic engineering ; Human papillomavirus ; Immortalization ; Mesenchymal stem cells ; Mutation ; p53 Protein ; Plasmids ; Precision medicine ; Regenerative medicine ; RNA-directed DNA polymerase ; Senescence ; Telomerase ; Telomerase reverse transcriptase ; Tumors</subject><ispartof>Journal of personalized medicine, 2023-11, Vol.13 (11), p.1621</ispartof><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-8c7e38effae69f314ddb4b760a2671e65da8440932e81b8caf816caaefbe0ef33</citedby><cites>FETCH-LOGICAL-c331t-8c7e38effae69f314ddb4b760a2671e65da8440932e81b8caf816caaefbe0ef33</cites><orcidid>0000-0002-9427-5739 ; 0000-0003-2961-0032</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Rakhmatullina, Aigul</creatorcontrib><creatorcontrib>Mingaleeva, Rimma</creatorcontrib><creatorcontrib>Gafurbaeva, Dina</creatorcontrib><creatorcontrib>Glazunova, Olesya</creatorcontrib><creatorcontrib>Sagdeeva, Aisylu</creatorcontrib><creatorcontrib>Bulatov, Emil</creatorcontrib><creatorcontrib>Rizvanov, Albert</creatorcontrib><creatorcontrib>Miftakhova, Regina</creatorcontrib><title>Adipose-Derived Mesenchymal Stem Cell (MSC) Immortalization by Modulation of hTERT and TP53 Expression Levels</title><title>Journal of personalized medicine</title><description>Mesenchymal stem cells (MSCs) are pivotal players in tissue repair and hold great promise as cell therapeutic agents for regenerative medicine. Additionally, they play a significant role in the development of various human diseases. Studies on MSC biology have encountered a limiting property of these cells, which includes a low number of passages and a decrease in differentiation potential during in vitro culture. Although common methods of immortalization through gene manipulations of cells are well established, the resulting MSCs vary in differentiation potential compared to primary cells and eventually undergo senescence. This study aimed to immortalize primary adipose-derived MSCs by overexpressing human telomerase reverse transcriptase (hTERT) gene combined with a knockdown of TP53. The research demonstrated that immortalized MSCs maintained a stable level of differentiation into osteogenic and chondrogenic lineages during 30 passages, while also exhibiting an increase in cell proliferation rate and differentiation potential towards the adipogenic lineage. Long-term culture of immortalized cells did not alter cell morphology and self-renewal potential. Consequently, a genetically stable line of immortalized adipose-derived MSCs (iMSCs) was established.</description><subject>Antigens</subject><subject>Bone marrow</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell division</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Cell self-renewal</subject><subject>Cytology</subject><subject>Fibroblasts</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Human papillomavirus</subject><subject>Immortalization</subject><subject>Mesenchymal stem cells</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Plasmids</subject><subject>Precision medicine</subject><subject>Regenerative medicine</subject><subject>RNA-directed DNA polymerase</subject><subject>Senescence</subject><subject>Telomerase</subject><subject>Telomerase reverse transcriptase</subject><subject>Tumors</subject><issn>2075-4426</issn><issn>2075-4426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpdkE1Lw0AQhhdRsNSe_AMLXioS3Y98bI4lVi20KDaewyaZpSnZbNxNivXXm1oPxYFhZpiHl5kXoWtK7jmPycO21ZRTSkNGz9CIkSjwfJ-F5yf9JZo4tyVDiICxkIyQnpVVaxx4j2CrHZR4BQ6aYrPXssbrDjROoK7xdLVObvFCa2M7WVffsqtMg_M9Xpmyr4-TUXiTzt9TLJsSp28Bx_Ov1oJzh-USdlC7K3ShZO1g8lfH6ONpniYv3vL1eZHMll7BOe08UUTABSglIYwVp35Z5n4ehUSyMKIQBqUUvk9izkDQXBRSCRoWUoLKgYDifIymR93Wms8eXJfpyhXDI7IB07uMiZgLn5Mhx-jmH7o1vW2G634pxuI4EgN1d6QKa5yzoLLWVlrafUZJdnA_O3Gf_wCu-Xbm</recordid><startdate>20231120</startdate><enddate>20231120</enddate><creator>Rakhmatullina, Aigul</creator><creator>Mingaleeva, Rimma</creator><creator>Gafurbaeva, Dina</creator><creator>Glazunova, Olesya</creator><creator>Sagdeeva, Aisylu</creator><creator>Bulatov, Emil</creator><creator>Rizvanov, Albert</creator><creator>Miftakhova, Regina</creator><general>MDPI AG</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9427-5739</orcidid><orcidid>https://orcid.org/0000-0003-2961-0032</orcidid></search><sort><creationdate>20231120</creationdate><title>Adipose-Derived Mesenchymal Stem Cell (MSC) Immortalization by Modulation of hTERT and TP53 Expression Levels</title><author>Rakhmatullina, Aigul ; 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subjects | Antigens Bone marrow Cancer therapies Cell culture Cell cycle Cell differentiation Cell division Cell growth Cell proliferation Cell self-renewal Cytology Fibroblasts Genes Genetic engineering Human papillomavirus Immortalization Mesenchymal stem cells Mutation p53 Protein Plasmids Precision medicine Regenerative medicine RNA-directed DNA polymerase Senescence Telomerase Telomerase reverse transcriptase Tumors |
title | Adipose-Derived Mesenchymal Stem Cell (MSC) Immortalization by Modulation of hTERT and TP53 Expression Levels |
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