PMID- 24309937
OWN - NLM
STAT- MEDLINE
DCOM- 20140612
LR  - 20220316
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 12
DP  - 2013 Dec 5
TI  - Long-term cultured mesenchymal stem cells frequently develop genomic mutations 
      but do not undergo malignant transformation.
PG  - e950
LID - 10.1038/cddis.2013.480 [doi]
AB  - Cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) are being tested 
      in several clinical trials and encouraging outcomes have been observed. To 
      determine whether in vitro expansion influences the genomic stability of 
      hUC-MSCs, we maintained nine hUC-MSC clones in long-term culture and 
      comparatively analyzed them at early and late passages. All of the clones 
      senesced in culture, exhibiting decreased telomerase activity and shortened 
      telomeres. Two clones showed no DNA copy number variations (CNVs) at passage 30 
      (P30). Seven clones had >/=1 CNVs at P30 compared with P3, and one of these clones 
      appeared trisomic chromosome 10 at the late passage. No tumor developed in 
      immunodeficient mice injected with hUC-MSCs, regardless of whether the cells had 
      CNVs at the late passage. mRNA-Seq analysis indicated that pathways of cell cycle 
      control and DNA damage response were downregulated during in vitro culture in 
      hUC-MSC clones that showed genomic instability, but the same pathways were 
      upregulated in the clones with good genomic stability. These results demonstrated 
      that hUC-MSCs can be cultured for many passages and attain a large number of 
      cells, but most of the cultured hUC-MSCs develop genomic alterations. Although 
      hUC-MSCs with genomic alterations do not undergo malignant transformation, 
      periodic genomic monitoring and donor management focusing on genomic stability 
      are recommended before these cells are used for clinical applications.
FAU - Wang, Y
AU  - Wang Y
AD  - State Key Laboratory of Experimental Hematology, National Engineering Research 
      Center of Stem Cells, Institute of Hematology and Hospital of Blood Diseases, 
      Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, 
      China.
FAU - Zhang, Z
AU  - Zhang Z
FAU - Chi, Y
AU  - Chi Y
FAU - Zhang, Q
AU  - Zhang Q
FAU - Xu, F
AU  - Xu F
FAU - Yang, Z
AU  - Yang Z
FAU - Meng, L
AU  - Meng L
FAU - Yang, S
AU  - Yang S
FAU - Yan, S
AU  - Yan S
FAU - Mao, A
AU  - Mao A
FAU - Zhang, J
AU  - Zhang J
FAU - Yang, Y
AU  - Yang Y
FAU - Wang, S
AU  - Wang S
FAU - Cui, J
AU  - Cui J
FAU - Liang, L
AU  - Liang L
FAU - Ji, Y
AU  - Ji Y
FAU - Han, Z-B
AU  - Han ZB
FAU - Fang, X
AU  - Fang X
FAU - Han, Z C
AU  - Han ZC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131205
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
SB  - IM
MH  - Cells, Cultured
MH  - DNA Copy Number Variations/genetics
MH  - Humans
MH  - Karyotype
MH  - Mesenchymal Stem Cells/*cytology/metabolism/*pathology
MH  - Mutation
MH  - Phylogeny
MH  - Telomere
PMC - PMC3877551
EDAT- 2013/12/07 06:00
MHDA- 2014/06/13 06:00
PMCR- 2013/12/01
CRDT- 2013/12/07 06:00
PHST- 2013/07/02 00:00 [received]
PHST- 2013/10/30 00:00 [revised]
PHST- 2013/10/31 00:00 [accepted]
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/06/13 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - cddis2013480 [pii]
AID - 10.1038/cddis.2013.480 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Dec 5;4(12):e950. doi: 10.1038/cddis.2013.480.