The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles

Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we stu...

Full description

Saved in:
Bibliographic Details
Main Authors: Angela Bentivegna, Gaia Roversi, Gabriele Riva, Laura Paoletta, Serena Redaelli, Mariarosaria Miloso, Giovanni Tredici, Leda Dalprà
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/5656701
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850120364204490752
author Angela Bentivegna
Gaia Roversi
Gabriele Riva
Laura Paoletta
Serena Redaelli
Mariarosaria Miloso
Giovanni Tredici
Leda Dalprà
author_facet Angela Bentivegna
Gaia Roversi
Gabriele Riva
Laura Paoletta
Serena Redaelli
Mariarosaria Miloso
Giovanni Tredici
Leda Dalprà
author_sort Angela Bentivegna
collection DOAJ
description Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic DNA in order to delineate a kind of methylation signature specific for early and late passages of culture. In the present work we focused on the modification of the methylation profiles of the X chromosome and imprinted loci, as sites expected to be more stable than whole genome. We propose a model where cultured hBM-MSCs undergo random modifications at the methylation level of most CGIs, nevertheless reflecting the original methylation status. We also pointed out global genome-wide demethylation connected to the long-term culture and senescence. Modification at CGIs promoters of specific genes could be related to the decrease in adipogenic differentiation potential. In conclusion, we showed important changes in CGIs methylation due to long-term in vitro culture that may affect the differentiation potential of hBM-MSCs. Therefore it is necessary to optimize the experimental conditions for in vitro expansion in order to minimize these epigenetic changes and to standardize safer procedures.
format Article
id doaj-art-61afa3f01dc14b6aa16e60a8ca5dacee
institution OA Journals
issn 1687-966X
1687-9678
language English
publishDate 2016-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-61afa3f01dc14b6aa16e60a8ca5dacee2025-08-20T02:35:22ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/56567015656701The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation ProfilesAngela Bentivegna0Gaia Roversi1Gabriele Riva2Laura Paoletta3Serena Redaelli4Mariarosaria Miloso5Giovanni Tredici6Leda Dalprà7School of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, ItalyHuman bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic DNA in order to delineate a kind of methylation signature specific for early and late passages of culture. In the present work we focused on the modification of the methylation profiles of the X chromosome and imprinted loci, as sites expected to be more stable than whole genome. We propose a model where cultured hBM-MSCs undergo random modifications at the methylation level of most CGIs, nevertheless reflecting the original methylation status. We also pointed out global genome-wide demethylation connected to the long-term culture and senescence. Modification at CGIs promoters of specific genes could be related to the decrease in adipogenic differentiation potential. In conclusion, we showed important changes in CGIs methylation due to long-term in vitro culture that may affect the differentiation potential of hBM-MSCs. Therefore it is necessary to optimize the experimental conditions for in vitro expansion in order to minimize these epigenetic changes and to standardize safer procedures.http://dx.doi.org/10.1155/2016/5656701
spellingShingle Angela Bentivegna
Gaia Roversi
Gabriele Riva
Laura Paoletta
Serena Redaelli
Mariarosaria Miloso
Giovanni Tredici
Leda Dalprà
The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
Stem Cells International
title The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
title_full The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
title_fullStr The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
title_full_unstemmed The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
title_short The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles
title_sort effect of culture on human bone marrow mesenchymal stem cells focus on dna methylation profiles
url http://dx.doi.org/10.1155/2016/5656701
work_keys_str_mv AT angelabentivegna theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT gaiaroversi theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT gabrieleriva theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT laurapaoletta theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT serenaredaelli theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT mariarosariamiloso theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT giovannitredici theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT ledadalpra theeffectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT angelabentivegna effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT gaiaroversi effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT gabrieleriva effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT laurapaoletta effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT serenaredaelli effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT mariarosariamiloso effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT giovannitredici effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles
AT ledadalpra effectofcultureonhumanbonemarrowmesenchymalstemcellsfocusondnamethylationprofiles