From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells
INTRODUCTION: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells that can differentiate into different cell lineages and have emerged as a promising tool for cell-targeted therapies and tissue engineering. Their use in a therapeutic context requires large-scale in vitro expansion, in...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580477/ https://www.ncbi.nlm.nih.gov/pubmed/23168092 http://dx.doi.org/10.1186/scrt138 |
_version_ | 1782260256850575360 |
---|---|
author | Redaelli, Serena Bentivegna, Angela Foudah, Dana Miloso, Mariarosaria Redondo, Juliana Riva, Gabriele Baronchelli, Simona Dalprà, Leda Tredici, Giovanni |
author_facet | Redaelli, Serena Bentivegna, Angela Foudah, Dana Miloso, Mariarosaria Redondo, Juliana Riva, Gabriele Baronchelli, Simona Dalprà, Leda Tredici, Giovanni |
author_sort | Redaelli, Serena |
collection | PubMed |
description | INTRODUCTION: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells that can differentiate into different cell lineages and have emerged as a promising tool for cell-targeted therapies and tissue engineering. Their use in a therapeutic context requires large-scale in vitro expansion, increasing the probability of genetic and epigenetic instabilities. Some evidence shows that an organized program of replicative senescence is triggered in human BM-MSCs (hBM-MSCs) on prolonged in vitro expansion that includes alterations in phenotype, differentiation potential, telomere length, proliferation rates, global gene-expression patterns, and DNA methylation profiles. METHODS: In this study, we monitored the chromosomal status, the biologic behavior, and the senescence state of hBM-MSCs derived from eight healthy donors at different passages during in vitro propagation. For a more complete picture, the telomere length was also monitored in five of eight donors, whereas the genomic profile was evaluated in three of eight donors by array-comparative genomic hybridization (array-CGH). Finally, an epigenomic profile was delineated and compared between early and late passages, by pooling DNA of hBM-MSCs from four donors. RESULTS: Our data indicate that long-term culture severely affects the characteristics of hBM-MSCs. All the observed changes (that is, enlarged morphology, decreased number of cell divisions, random loss of genomic regions, telomere shortening) might be regulated by epigenetic modifications. Gene Ontology analysis revealed that specific biologic processes of hBM-MSCs are affected by variations in DNA methylation from early to late passages. CONCLUSIONS: Because we revealed a significant decrease in DNA methylation levels in hBM-MSCs during long-term culture, it is very important to unravel how these modifications can influence the biologic features of hBM-MSCs to keep track of this organized program and also to clarify the conflicting observations on hBM-MSC malignant transformation in the literature. |
format | Online Article Text |
id | pubmed-3580477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35804772013-03-04 From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells Redaelli, Serena Bentivegna, Angela Foudah, Dana Miloso, Mariarosaria Redondo, Juliana Riva, Gabriele Baronchelli, Simona Dalprà, Leda Tredici, Giovanni Stem Cell Res Ther Research INTRODUCTION: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells that can differentiate into different cell lineages and have emerged as a promising tool for cell-targeted therapies and tissue engineering. Their use in a therapeutic context requires large-scale in vitro expansion, increasing the probability of genetic and epigenetic instabilities. Some evidence shows that an organized program of replicative senescence is triggered in human BM-MSCs (hBM-MSCs) on prolonged in vitro expansion that includes alterations in phenotype, differentiation potential, telomere length, proliferation rates, global gene-expression patterns, and DNA methylation profiles. METHODS: In this study, we monitored the chromosomal status, the biologic behavior, and the senescence state of hBM-MSCs derived from eight healthy donors at different passages during in vitro propagation. For a more complete picture, the telomere length was also monitored in five of eight donors, whereas the genomic profile was evaluated in three of eight donors by array-comparative genomic hybridization (array-CGH). Finally, an epigenomic profile was delineated and compared between early and late passages, by pooling DNA of hBM-MSCs from four donors. RESULTS: Our data indicate that long-term culture severely affects the characteristics of hBM-MSCs. All the observed changes (that is, enlarged morphology, decreased number of cell divisions, random loss of genomic regions, telomere shortening) might be regulated by epigenetic modifications. Gene Ontology analysis revealed that specific biologic processes of hBM-MSCs are affected by variations in DNA methylation from early to late passages. CONCLUSIONS: Because we revealed a significant decrease in DNA methylation levels in hBM-MSCs during long-term culture, it is very important to unravel how these modifications can influence the biologic features of hBM-MSCs to keep track of this organized program and also to clarify the conflicting observations on hBM-MSC malignant transformation in the literature. BioMed Central 2012-11-20 /pmc/articles/PMC3580477/ /pubmed/23168092 http://dx.doi.org/10.1186/scrt138 Text en Copyright ©2012 Redaelli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Redaelli, Serena Bentivegna, Angela Foudah, Dana Miloso, Mariarosaria Redondo, Juliana Riva, Gabriele Baronchelli, Simona Dalprà, Leda Tredici, Giovanni From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title | From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title_full | From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title_fullStr | From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title_full_unstemmed | From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title_short | From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
title_sort | from cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580477/ https://www.ncbi.nlm.nih.gov/pubmed/23168092 http://dx.doi.org/10.1186/scrt138 |
work_keys_str_mv | AT redaelliserena fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT bentivegnaangela fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT foudahdana fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT milosomariarosaria fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT redondojuliana fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT rivagabriele fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT baronchellisimona fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT dalpraleda fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells AT tredicigiovanni fromcytogenomictoepigenomicprofilesmonitoringthebiologicbehaviorofinvitroculturedhumanbonemarrowmesenchymalstemcells |