DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?

Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associa...

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Main Authors: Angela Bentivegna, Mariarosaria Miloso, Gabriele Riva, Dana Foudah, Valentina Butta, Leda Dalprà, Giovanni Tredici
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2013/192425
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author Angela Bentivegna
Mariarosaria Miloso
Gabriele Riva
Dana Foudah
Valentina Butta
Leda Dalprà
Giovanni Tredici
author_facet Angela Bentivegna
Mariarosaria Miloso
Gabriele Riva
Dana Foudah
Valentina Butta
Leda Dalprà
Giovanni Tredici
author_sort Angela Bentivegna
collection DOAJ
description Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs during ex vivo expansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability.
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institution Kabale University
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publishDate 2013-01-01
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series Stem Cells International
spelling doaj-art-d9dfd124b54e40ec8a49ed0be8272e1a2025-08-20T03:24:24ZengWileyStem Cells International1687-966X1687-96782013-01-01201310.1155/2013/192425192425DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?Angela Bentivegna0Mariarosaria Miloso1Gabriele Riva2Dana Foudah3Valentina Butta4Leda Dalprà5Giovanni Tredici6Department of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyDepartment of Surgery and Interdisciplinary Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, ItalyMesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs during ex vivo expansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability.http://dx.doi.org/10.1155/2013/192425
spellingShingle Angela Bentivegna
Mariarosaria Miloso
Gabriele Riva
Dana Foudah
Valentina Butta
Leda Dalprà
Giovanni Tredici
DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
Stem Cells International
title DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
title_full DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
title_fullStr DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
title_full_unstemmed DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
title_short DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
title_sort dna methylation changes during in vitro propagation of human mesenchymal stem cells implications for their genomic stability
url http://dx.doi.org/10.1155/2013/192425
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