PMID- 17514511
OWN - NLM
STAT- MEDLINE
DCOM- 20070924
LR  - 20211203
IS  - 1071-2690 (Print)
IS  - 1071-2690 (Linking)
VI  - 43
IP  - 3-4
DP  - 2007 Mar-Apr
TI  - Chromosomal instability in human mesenchymal stem cells immortalized with human 
      papilloma virus E6, E7, and hTERT genes.
PG  - 129-38
AB  - Human mesenchymal stem cells (hMSCs) are expected to be an enormous potential 
      source for future cell therapy, because of their self-renewing divisions and also 
      because of their multiple-lineage differentiation. The finite lifespan of these 
      cells, however, is a hurdle for clinical application. Recently, several hMSC 
      lines have been established by immortalized human telomerase reverse 
      transcriptase gene (hTERT) alone or with hTERT in combination with human 
      papillomavirus type 16 E6/E7 genes (E6/E7) and human proto-oncogene, Bmi-1, but 
      have not so much been characterized their karyotypic stability in detail during 
      extended lifespan under in vitro conditions. In this report, the cells 
      immortalized with the hTERT gene alone exhibited little change in karyotype, 
      whereas the cells immortalized with E6/E7 plus hTERT genes or Bmi-1, E6 plus 
      hTERT genes were unstable regarding chromosome numbers, which altered markedly 
      during prolonged culture. Interestingly, one unique chromosomal alteration was 
      the preferential loss of chromosome 13 in three cell lines, observed by 
      fluorescence in situ hybridization (FISH) and comparative-genomic hybridization 
      (CGH) analysis. The four cell lines all maintained the ability to differentiate 
      into both osteogenic and adipogenic lineages, and two cell lines underwent 
      neuroblastic differentiation. Thus, our results were able to provide a step 
      forward toward fulfilling the need for a sufficient number of cells for new 
      therapeutic applications, and substantiate that these cell lines are a useful 
      model for understanding the mechanisms of chromosomal instability and 
      differentiation of hMSCs.
FAU - Takeuchi, Masao
AU  - Takeuchi M
AD  - Division of Bioresources, National Institute of Biomedical Innovation, Osaka, 
      Japan. takeuchim@nibio.go.jp
FAU - Takeuchi, Kikuko
AU  - Takeuchi K
FAU - Kohara, Arihiro
AU  - Kohara A
FAU - Satoh, Motonobu
AU  - Satoh M
FAU - Shioda, Setsuko
AU  - Shioda S
FAU - Ozawa, Yutaka
AU  - Ozawa Y
FAU - Ohtani, Azusa
AU  - Ohtani A
FAU - Morita, Keiko
AU  - Morita K
FAU - Hirano, Takashi
AU  - Hirano T
FAU - Terai, Masanori
AU  - Terai M
FAU - Umezawa, Akihiro
AU  - Umezawa A
FAU - Mizusawa, Hiroshi
AU  - Mizusawa H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070521
PL  - Germany
TA  - In Vitro Cell Dev Biol Anim
JT  - In vitro cellular & developmental biology. Animal
JID - 9418515
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
EIN - In Vitro Cell Dev Biol Anim. 2007 May-Jun;43(5-6):202
EIN - In Vitro Cell Dev Biol Anim. 2007 Sep-Oct;43(8-9):315-8
MH  - Cell Culture Techniques
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cell Lineage
MH  - *Chromosomal Instability
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Mesenchymal Stem Cells/cytology/*ultrastructure
MH  - Oncogene Proteins, Viral/*genetics
MH  - Papillomavirus E7 Proteins
MH  - Proto-Oncogene Mas
MH  - Repressor Proteins/*genetics
MH  - Telomerase/*genetics
EDAT- 2007/05/22 09:00
MHDA- 2007/09/25 09:00
CRDT- 2007/05/22 09:00
PHST- 2007/01/25 00:00 [received]
PHST- 2007/03/27 00:00 [accepted]
PHST- 2007/05/22 09:00 [pubmed]
PHST- 2007/09/25 09:00 [medline]
PHST- 2007/05/22 09:00 [entrez]
AID - 10.1007/s11626-007-9021-9 [doi]
PST - ppublish
SO  - In Vitro Cell Dev Biol Anim. 2007 Mar-Apr;43(3-4):129-38. doi: 
      10.1007/s11626-007-9021-9. Epub 2007 May 21.