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.

Bentivegna, A., Roversi, G., Riva, G., Paoletta, L., Redaelli, S., Miloso, M., et al. (2016). The effect of culture on human bone marrow mesenchymal stem cells: Focus on DNA methylation profiles. STEM CELLS INTERNATIONAL, 2016 [10.1155/2016/5656701].

The effect of culture on human bone marrow mesenchymal stem cells: Focus on DNA methylation profiles

BENTIVEGNA, ANGELA
Primo
;
ROVERSI, GAIA;RIVA, GABRIELE;REDAELLI, SERENA;MILOSO, MARIAROSARIA;TREDICI, GIOVANNI;DALPRA', LEDA
2016

Abstract

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.
Articolo in rivista - Articolo scientifico
Human Bone Marrow Mesenchymal Stem Cells, DNA Methylation
English
12
Bentivegna, A., Roversi, G., Riva, G., Paoletta, L., Redaelli, S., Miloso, M., et al. (2016). The effect of culture on human bone marrow mesenchymal stem cells: Focus on DNA methylation profiles. STEM CELLS INTERNATIONAL, 2016 [10.1155/2016/5656701].
File in questo prodotto:
File Dimensione Formato  
5656701.pdf

accesso aperto

Dimensione 7.54 MB
Formato Adobe PDF
7.54 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/102786
Citazioni
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 18
Social impact