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
Hauptverfasser: Rakhmatullina, Aigul, Mingaleeva, Rimma, Gafurbaeva, Dina, Glazunova, Olesya, Sagdeeva, Aisylu, Bulatov, Emil, Rizvanov, Albert, Miftakhova, Regina
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container_issue 11
container_start_page 1621
container_title Journal of personalized medicine
container_volume 13
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. 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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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