Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into multiple cell types. Accumulating preclinical and clinical evidence indicates that MSCs are good candidates to use as cell therapy in many degenerative diseases. For MSC clinical applications, an adequate number of cells are necessary so an extensive expansion is required. However, spontaneous immortalization and malignant transformation of MSCs after culture expansion have been reported in human and mouse, while very few data are present for rat MSCs (rMSCs). In this study, we monitored the chromosomal status of rMSCs at several passages in vitro, also testing the influence of four different cell culture conditions. We first used the conventional traditional cytogenetic techniques, in order to have the opportunity to observe even minor structural abnormalities and to identify low-degree mosaic conditions. Then, a more detailed genomic analysis was conducted by array comparative genomic hybridization. We demonstrated that, irrespective of culture conditions, rMSCs manifested a markedly aneuploid karyotype and a progressive chromosomal instability in all the passages we analyzed and that they are anything but stable during in vitro culture. Despite the fact that the risk of neoplastic transformation associated with this genomic instability needs to be further addressed and considering the apparent genomic stability reported for in vitro cultured human MSCs (hMSCs), our findings underline the fact that rMSCs may not in fact be a good model for effectively exploring the full clinical therapeutic potential of hMSCs.

Foudah, D., Redaelli, S., Donzelli, E., Bentivegna, A., Miloso, M., Dalpra', L., et al. (2009). Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells. CHROMOSOME RESEARCH, 17, 1025-1039 [10.1007/s10577-009-9090-6].

Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells

FOUDAH, DANA;REDAELLI, SERENA;DONZELLI, ELISABETTA;BENTIVEGNA, ANGELA;MILOSO, MARIAROSARIA;DALPRA', LEDA;TREDICI, GIOVANNI
2009

Abstract

Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into multiple cell types. Accumulating preclinical and clinical evidence indicates that MSCs are good candidates to use as cell therapy in many degenerative diseases. For MSC clinical applications, an adequate number of cells are necessary so an extensive expansion is required. However, spontaneous immortalization and malignant transformation of MSCs after culture expansion have been reported in human and mouse, while very few data are present for rat MSCs (rMSCs). In this study, we monitored the chromosomal status of rMSCs at several passages in vitro, also testing the influence of four different cell culture conditions. We first used the conventional traditional cytogenetic techniques, in order to have the opportunity to observe even minor structural abnormalities and to identify low-degree mosaic conditions. Then, a more detailed genomic analysis was conducted by array comparative genomic hybridization. We demonstrated that, irrespective of culture conditions, rMSCs manifested a markedly aneuploid karyotype and a progressive chromosomal instability in all the passages we analyzed and that they are anything but stable during in vitro culture. Despite the fact that the risk of neoplastic transformation associated with this genomic instability needs to be further addressed and considering the apparent genomic stability reported for in vitro cultured human MSCs (hMSCs), our findings underline the fact that rMSCs may not in fact be a good model for effectively exploring the full clinical therapeutic potential of hMSCs.
Articolo in rivista - Articolo scientifico
Cytogenetic analysis, rat mesenchymal stem cells, chromosomal status, genomic stability, in vitro culture conditions, MSCs differentiation capacity
English
2009
17
1025
1039
none
Foudah, D., Redaelli, S., Donzelli, E., Bentivegna, A., Miloso, M., Dalpra', L., et al. (2009). Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells. CHROMOSOME RESEARCH, 17, 1025-1039 [10.1007/s10577-009-9090-6].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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/10281/8749
Citazioni
  • Scopus 74
  • ???jsp.display-item.citation.isi??? 72
Social impact