Cited by 246Pluripotent Stem Cells ResearchCell death mechanisms and regulationMesenchymal stem cell research

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Inhibition of pluripotent stem cell-derived teratoma formation by small molecules

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Lee, Mi-Ok, Moon, Sung Hwan, Jeong, Ho-Chang, Yi, Ji-Yeon, Lee, Tae-Hee, Shim, Sung Han, Rhee, Yong-Hee, Lee, Sang-Hun, Oh, Seok-Jeong, Lee, Moo-Yeol, Han, Min-Joon, Cho, Yee Sook, Chung, Hyung-Min, Kim, Kwang-Soo, Cha, Hyuk-Jin·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1303669110PMC PMC3761568

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Abstract

The future of safe cell-based therapy rests on overcoming teratoma/tumor formation, in particular when using human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Because the presence of a few remaining undifferentiated hPSCs can cause undesirable teratomas after transplantation, complete removal of these cells with no/minimal damage to differentiated cells is a prerequisite for clinical application of hPSC-based therapy. Having identified a unique hESC signature of pro- and antiapoptotic gene expression profile, we hypothesized that targeting hPSC-specific antiapoptotic factor(s) (i.e., survivin or Bcl10) represents an efficient strategy to selectively eliminate pluripotent cells with teratoma potential. Here we report the successful identification of small molecules that can effectively inhibit these antiapoptotic factors, leading to selective and efficient removal of pluripotent stem cells through apoptotic cell death. In particular, a single treatment of hESC-derived mixed population with chemical inhibitors of survivin (e.g., quercetin or YM155) induced selective and complete cell death of undifferentiated hPSCs. In contrast, differentiated cell types (e.g., dopamine neurons and smooth-muscle cells) derived from hPSCs survived well and maintained their functionality. We found that quercetin-induced selective cell death is caused by mitochondrial accumulation of p53 and is sufficient to prevent…

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Background

Authors: Lee, M.-O., Moon, S. H., Jeong, H.-C., Yi, J.-Y., Lee, T.-H., Shim, S. H., Rhee, Y.-H., Lee, S.-H., Oh, S.-J., Lee, M.-Y., Han, M.-J., Cho, Y. S., Chung, H.-M., Kim, K.-S., & Cha, H.-J.
Affiliations: Sogang University (KR)
CHA University (KR)
Sejong University (KR)
Hanyang University (KR)
Dongguk University (KR)
Harvard University (US)
Korea Research Institute of Bioscience and Biotechnology (KR)
Konkuk University (KR)
ORCID: Lee, Mi-Ok
Moon, Sung Hwan
Jeong, Ho-Chang
Lee, Tae-Hee
Shim, Sung Han
Lee, Sang-Hun
Lee, Moo-Yeol
Han, Min-Joon
Cho, Yee Sook
Chung, Hyung-Min
Kim, Kwang-Soo
Cha, Hyuk-Jin
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2013-08-05
Volume: 110
Issue: 35
Pages: E3281-90
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1303669110
PMC: PMC3761568
OpenAlex: W2065594892
Cited by: 246
References: 68
Citations by year: 2026: 5 · 2025: 12 · 2024: 18 · 2023: 15 · 2022: 16 · 2021: 21 · 2020: 19 · 2019: 22 · 2018: 16 · 2017: 21 · 2016: 32 · 2015: 24 · 2014: 20 · 2013: 5
FWCI: 12.10
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
KRIBB Repository (submittedVersion)
Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS070577, NS070577)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: teratoma prevention, human pluripotent stem cells, human embryonic stem cells, human induced pluripotent stem cells, small molecule inhibitors, survivin, BCL10, quercetin, YM155, selective cell death, apoptosis, p53, dopaminergic neurons, smooth muscle cells
MeSH terms: B-Cell CLL-Lymphoma 10 Protein, Survivin, Cell Differentiation, Cells, Cultured, Humans, Imidazoles, Mitochondria, Naphthoquinones, Teratoma, Tumor Suppressor Protein p53, Apoptosis, Gene Expression Profiling, Stem Cell Transplantation, Pluripotent Stem Cells, Adaptor Proteins, Signal Transducing, Inhibitor of Apoptosis Proteins, Small Molecule Libraries

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Inhibition of pluripotent stem cell-derived teratoma formation by small molecules

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