Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) to Monitor Compound Effects on Cardiac Myocyte Signaling Pathways

Current Protocols in Chemical Biology
Liang GuoMyrtle Davis

Abstract

There is a need to develop mechanism-based assays to better inform risk of cardiotoxicity. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are rapidly gaining acceptance as a biologically relevant in vitro model for use in drug discovery and cardiotoxicity screens. Utilization of hiPSC-CMs for mechanistic investigations would benefit from confirmation of the expression and activity of cellular pathways that are known to regulate cardiac myocyte viability and function. This unit describes an approach to demonstrate the presence and function of signaling pathways in hiPSC-CMs and the effects of treatments on these pathways. We present a workflow that employs protocols to demonstrate protein expression and functional integrity of signaling pathway(s) of interest and to characterize biological consequences of signaling modulation. These protocols utilize a unique combination of structural, functional, and biochemical endpoints to interrogate compound effects on cardiomyocytes.

References

Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·H TakaishiY Nishizuka
Apr 30, 2002·Gan to kagaku ryoho. Cancer & chemotherapy·Yutaka TokudaTomoo Tajima
Sep 19, 2002·Cancer·Deborah L Keefe
Oct 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Roger A O'NeillPeter B Vander Horn
Nov 22, 2007·Science·Junying YuJames A Thomson
Feb 12, 2008·Current Protocols in Molecular Biology·Mary C Phelan
Apr 24, 2008·Journal of Molecular and Cellular Cardiology·Stephen J FullerPeter H Sugden
Jul 31, 2009·Cancer Treatment Reviews·Hamdy AzimBernard Escudier
Aug 28, 2009·The New England Journal of Medicine·Tobias ReichlinChristian Mueller
Dec 17, 2009·Journal of the National Cancer Institute·Adriana AlbiniDouglas M Noonan
Apr 3, 2010·BioTechniques·Jennifer BordeauxDavid Rimm
Aug 24, 2010·Progress in Cardiovascular Diseases·Giuseppe CuriglianoAron Goldhirsch
Dec 4, 2010·Cancer Treatment Reviews·Elżbieta Senkus, Jacek Jassem
Dec 15, 2010·The Breast : Official Journal of the European Society of Mastology·Alberto ZambelliAlberto Riccardi
Dec 24, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Howard R MellorRuth R A Roberts
Jun 23, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liang GuoKyle L Kolaja
Jul 12, 2011·Physiological Reviews·Mark A SussmanMichael McGregor
Sep 6, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Junyi MaCraig T January
Nov 5, 2011·Stem Cells and Development·Joshua E BabiarzKyle L Kolaja
Nov 25, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yi-Yun KaoPei-Shan Liu
Jan 25, 2012·Pharmacology & Therapeutics·Naama Zeevi-LevinOfer Binah
Mar 20, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Brian Wadugu, Bernhard Kühn
Jun 8, 2012·Breast Cancer Research and Treatment·Carmine FedeleClaudia De Lorenzo
Jul 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Payal RanaYvonne Will
Aug 1, 2012·British Journal of Pharmacology·Jaffar M KhanSian E Harding
Sep 6, 2012·Journal of the National Cancer Institute·Erin J Aiello BowlesUNKNOWN Pharmacovigilance Study Team
Sep 14, 2012·Journal of Biomolecular Screening·Oksana SirenkoEvan F Cromwell
Sep 18, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dinesh PuppalaSandra J Engle
Sep 28, 2012·Frontiers in Physiology·Maaike HoekstraArie O Verkerk
Dec 25, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Karen SchweikartMyrtle Davis
Jan 15, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amy PointonJames E Sidaway
Mar 7, 2013·Stem Cells and Development·Scott D LundyMichael A Laflamme
Mar 9, 2013·Toxicology Letters·Clay W ScottYvonne P Dragan
Apr 3, 2013·Methods in Molecular Biology·Paul W Burridge, Elias T Zambidis
May 28, 2013·Toxicology and Applied Pharmacology·Kimberly R DohertySarah Bacus
Jul 9, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Christine Y IvashchenkoRobert N Willette

❮ Previous
Next ❯

Citations

Dec 2, 2015·Chemical Research in Toxicology·Donna M DambachDolores Diaz
Oct 11, 2016·Frontiers in Physiology·Mayra de A Marques, Guilherme A P de Oliveira
Mar 10, 2016·Biochimica Et Biophysica Acta·Juan C Del ÁlamoMark Mercola
Aug 5, 2016·International Journal of Molecular Sciences·Qiao ZhangYanjiang Qiao
Nov 23, 2017·Drug and Chemical Toxicology·Simon LoiodiceFranck Atienzar
Jun 13, 2015·Current Protocols in Mouse Biology·Brandi L Carofino, Monica J Justice
Feb 16, 2019·Cardiovascular Research·Nazish SayedJoseph C Wu
Mar 2, 2017·World Journal of Clinical Oncology·Tia HarmonRuben R Gonzalez-Perez
Aug 26, 2016·Journal of Toxicologic Pathology·Ryota TochinaiMasayoshi Kuwahara
Sep 21, 2018·Experimental and Therapeutic Medicine·Feng ZhangChengzhi Lu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiotoxicity

Cardiotoxicity refers to the muscle damage or dysfunction of heart electrophysiology caused by drug intake or due to disease complications. It is a well-known side effect of several cytotoxic drugs, especially of the anthracyclines and can lead to long term morbidity. Here is the latest research.