An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation
In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issu...
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MDPI AG
2023-05-01
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| Series: | Nutrients |
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| author | Aeyung Kim Su-Jin Baek Sarah Shin Seo-Young Lee Sun-Ku Chung |
| author_facet | Aeyung Kim Su-Jin Baek Sarah Shin Seo-Young Lee Sun-Ku Chung |
| author_sort | Aeyung Kim |
| collection | DOAJ |
| description | In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation. |
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| last_indexed | 2024-03-11T03:25:45Z |
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| spelling | doaj.art-b5755196bae84768959022b86f22af5d2023-11-18T02:45:21ZengMDPI AGNutrients2072-66432023-05-011510236410.3390/nu15102364An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma FormationAeyung Kim0Su-Jin Baek1Sarah Shin2Seo-Young Lee3Sun-Ku Chung4Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaKM Data Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaIn cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation.https://www.mdpi.com/2072-6643/15/10/2364<i>Coptidis rhizoma</i>induced pluripotent stem cellsapoptosisteratomagenotoxicity |
| spellingShingle | Aeyung Kim Su-Jin Baek Sarah Shin Seo-Young Lee Sun-Ku Chung An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation Nutrients <i>Coptidis rhizoma</i> induced pluripotent stem cells apoptosis teratoma genotoxicity |
| title | An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation |
| title_full | An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation |
| title_fullStr | An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation |
| title_full_unstemmed | An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation |
| title_short | An Ethanol Extract of <i>Coptidis rhizoma</i> Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation |
| title_sort | ethanol extract of i coptidis rhizoma i induces apoptotic cell death in induced pluripotent stem cells and suppresses teratoma formation |
| topic | <i>Coptidis rhizoma</i> induced pluripotent stem cells apoptosis teratoma genotoxicity |
| url | https://www.mdpi.com/2072-6643/15/10/2364 |
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