期刊
CELL DEATH & DISEASE
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2013.480
关键词
mesenchymal stem cells; array-based comparative genomic hybridization; copy number variations; mRNA-Seq
类别
资金
- National Natural Science Foundation of China [81330015, 31371300]
- 863 project [2011AA020118, 2012AA022502]
- Ministry of Science and Technology of China [2011 CB964800, 2011CB964802, 2012BAH35F03-11]
- Chinese Academy of Sciences, Stem Cell and Regenerative Medicine Research [XDA01040405]
- National Key Scientific Instrument and Equipment Development Projects [2011YQ03013404]
- Tianjin Sci-Tech Support Plan [13ZCZDSY02200]
- Major Projects of independent innovation in Binhai New Area [2012-BK120022]
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.
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