scholarly journals Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells

2018 ◽  
Vol 92 (4) ◽  
pp. 1507-1524 ◽  
Author(s):  
Harshal Nemade ◽  
Umesh Chaudhari ◽  
Aviseka Acharya ◽  
Jürgen Hescheler ◽  
Jan Georg Hengstler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Pluripotent Stem Cells ◽  
Cancer Drug ◽  
Human Cardiomyocytes ◽  
Anti Cancer ◽  
Cell Death Mechanisms

scholarly journals Scarless Enriched selection of Genome edited Human Pluripotent Stem Cells Using Induced Drug Resistance

2019 ◽  
Author(s):  
Keun-Tae Kim ◽  
Ju-Chan Park ◽  
Haeseung Lee ◽  
Hyeon-Ki Jang ◽  
Yan Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Gene Editing ◽  
Human Pluripotent Stem Cells ◽  
Cancer Drug ◽  
Efficient Gene ◽  
Anti Cancer ◽  
Low Efficiency ◽  
High Cytotoxicity ◽  
Selection Of

SummaryAn efficient gene editing technique for use in human pluripotent stem cells (hPSCs) would have great potential value in regenerative medicine, as well as in drug discovery based on isogenic human disease models. However, the extremely low efficiency of gene editing in hPSCs is a major technical hurdle that remains to be resolved. Previously, we demonstrated that YM155, a survivin inhibitor developed as an anti-cancer drug, induces highly selective cell death in undifferentiated hPSCs. In this study, we demonstrated that the high cytotoxicity of YM155 in hPSCs, which is mediated by selective cellular uptake of the drug, is due to high expression of SLC35F2 in these cells. Consistent with this, knockout of SLC35F2 with CRISPR-Cas9 or depletion with siRNAs made hPSCs highly resistant to YM155. Simultaneous gene editing of a gene of interest and transient knockdown of SLC35F2 following YM155 treatment enabled genome-edited hPSCs to survive because YM155 resistance was temporarily induced, thereby achieving enriched selection of genome-edited clonal populations. This precise and efficient genome editing approach took as little as 3 weeks without cell sorting or introduction of additional genes.

Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II

2011 ◽  
Vol 82 (12) ◽  
pp. 1843-1852 ◽  
Author(s):  
Viviane Brel ◽  
Jean-Philippe Annereau ◽  
Stéphane Vispé ◽  
Anna Kruczynski ◽  
Christian Bailly ◽  
...  
Keyword(s):  
Cell Death ◽  
Topoisomerase Ii ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cell Death Mechanisms

scholarly journals Suppressing Pyroptosis Augments Post-Transplant Survival of Stem Cells and Cardiac Function Following Ischemic Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 7946
Author(s):  
Chang Youn Lee ◽  
Seahyoung Lee ◽  
Seongtae Jeong ◽  
Jiyun Lee ◽  
Hyang-Hee Seo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Transplant Survival ◽  
Post Transplant ◽  
Heart Functions ◽  
Cell Death Mechanisms

The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1b production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.

scholarly journals Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells

2011 ◽  
Vol 91 (4) ◽  
pp. 577-586 ◽  
Author(s):  
Ashish Mehta ◽  
Ying Ying Chung ◽  
Alvin Ng ◽  
Fahamy Iskandar ◽  
Shirhan Atan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Cardiomyocytes ◽  
Pharmacological Response ◽  
Induced Pluripotent

Research and Findings

2010 ◽  
Vol 14 (02) ◽  
pp. 36-39
Keyword(s):  
Stem Cells ◽  
Vitamin E ◽  
Pluripotent Stem Cells ◽  
Islet Cell ◽  
Malaria Parasite ◽  
Differentiated Cells ◽  
Anti Cancer ◽  
Root Weevils ◽  
Depth Study ◽  
Clover Root

Singapore Scientists Discover New Concoction to Reprogram Differentiated Cells into Pluripotent Stem Cells. NTU Researchers Complete the World's First in-depth Study of the Malaria Parasite Genome. Cause of Islet Cell Rejection Discovered. Scientist Develops Anti-Cancer Derivative of Vitamin E. Destructive Clover Root Weevils Found.

scholarly journals Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Luciana Isaja ◽  
Sofía Mucci ◽  
Jonathan Vera ◽  
María Soledad Rodríguez-Varela ◽  
Mariela Marazita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Cell Viability ◽  
Pluripotent Stem Cells ◽  
Chromatin Condensation ◽  
Human Pluripotent Stem Cells ◽  
Chemical Hypoxia ◽  
Wide Range ◽  
Independent Mechanism ◽  
Induced Pluripotent

AbstractHuman embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O2). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl2 and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl2 and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.

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