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Stem Cell Res Ther. 2017 Nov 2;8(1):245. doi: 10.1186/s13287-017-0698-8.

Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

Author information

1
Guangzhou Biocare Institute of Cancer, Building D, Guangzhou International Business Incubator, No. 3, Juquan Road, Guangzhou Science Park, Guangzhou, 510663, Guangdong, People's Republic of China. linli_wang@163.com.
2
Guangzhou Biocare Institute of Cancer, Building D, Guangzhou International Business Incubator, No. 3, Juquan Road, Guangzhou Science Park, Guangzhou, 510663, Guangdong, People's Republic of China.
3
The Guangdong Key Lab for Shock and Microcirculation Research, Departments of Pathophysiology, Southern Medical University, Guangzhou, 510515, People's Republic of China.
4
State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Centre, Guangzhou, 510060, People's Republic of China.
5
Guangzhou Biocare Institute of Cancer, Building D, Guangzhou International Business Incubator, No. 3, Juquan Road, Guangzhou Science Park, Guangzhou, 510663, Guangdong, People's Republic of China. lijun37@mail.sysu.edu.cn.
6
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Yuexiu District, Guangzhou, Guangdong, 510080, China. lijun37@mail.sysu.edu.cn.

Abstract

BACKGROUND:

Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important.

METHODS:

To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses.

RESULTS:

We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system.

CONCLUSION:

The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

KEYWORDS:

6F/BM1-4C system; Human urinary cells; Induced pluripotent stem cells; iPSC safety

PMID:
29096702
PMCID:
PMC5667457
DOI:
10.1186/s13287-017-0698-8
[Indexed for MEDLINE]
Free PMC Article

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