Anton Deicher1, Timon Seeger2,3. 1. Department of Internal Medicine III, University Hospital Heidelberg, INF 410, 69126, Heidelberg, Germany. 2. Department of Internal Medicine III, University Hospital Heidelberg, INF 410, 69126, Heidelberg, Germany. timon.seeger@med.uni-heidelberg.de. 3. German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, Germany. timon.seeger@med.uni-heidelberg.de.
Abstract
PURPOSE OF REVIEW: Heart failure is among the most prevalent disease complexes overall and is associated with high morbidity and mortality. The underlying aetiology is manifold including coronary artery disease, genetic alterations and mutations, viral infections, adverse immune responses, and cardiac toxicity. To date, no specific therapies have been developed despite notable efforts. This can especially be attributed to hurdles in translational research, mainly due to the lack of proficient models of heart failure limited translation of therapeutic approaches from bench to bedside. RECENT FINDINGS: Human induced pluripotent stem cells (hiPSCs) are rising in popularity, granting the ability to divide infinitely, to hold human, patient-specific genome, and to differentiate into any human cell, including cardiomyocytes (hiPSC-CMs). This brings magnificent promise to cardiological research, providing the possibility to recapitulate cardiac diseases in a dish. Advances in yield, maturity, and in vivo resemblance due to straightforward, low-cost protocols, high-throughput approaches, and complex 3D cultures have made this tool widely applicable. In recent years, hiPSC-CMs have been used to model a wide variety of cardiac diseases, bringing along the possibility to not only elucidate molecular mechanisms but also to test novel therapeutic approaches in the dish. Within the last decade, hiPSC-CMs have been exponentially employed to model heart failure. Constant advancements are aiming at improvements of differentiation protocols, hiPSC-CM maturity, and assays to elucidate molecular mechanisms and cellular functions. However, hiPSC-CMs are remaining relatively immature, and in vitro models can only partially recapitulate the complex interactions in vivo. Nevertheless, hiPSC-CMs have evolved as an essential model system in cardiovascular research.
PURPOSE OF REVIEW: Heart failure is among the most prevalent disease complexes overall and is associated with high morbidity and mortality. The underlying aetiology is manifold including coronary artery disease, genetic alterations and mutations, viral infections, adverse immune responses, and cardiac toxicity. To date, no specific therapies have been developed despite notable efforts. This can especially be attributed to hurdles in translational research, mainly due to the lack of proficient models of heart failure limited translation of therapeutic approaches from bench to bedside. RECENT FINDINGS:Human induced pluripotent stem cells (hiPSCs) are rising in popularity, granting the ability to divide infinitely, to hold human, patient-specific genome, and to differentiate into any human cell, including cardiomyocytes (hiPSC-CMs). This brings magnificent promise to cardiological research, providing the possibility to recapitulate cardiac diseases in a dish. Advances in yield, maturity, and in vivo resemblance due to straightforward, low-cost protocols, high-throughput approaches, and complex 3D cultures have made this tool widely applicable. In recent years, hiPSC-CMs have been used to model a wide variety of cardiac diseases, bringing along the possibility to not only elucidate molecular mechanisms but also to test novel therapeutic approaches in the dish. Within the last decade, hiPSC-CMs have been exponentially employed to model heart failure. Constant advancements are aiming at improvements of differentiation protocols, hiPSC-CM maturity, and assays to elucidate molecular mechanisms and cellular functions. However, hiPSC-CMs are remaining relatively immature, and in vitro models can only partially recapitulate the complex interactions in vivo. Nevertheless, hiPSC-CMs have evolved as an essential model system in cardiovascular research.
Authors: Timon Seeger; Rajani Shrestha; Chi Keung Lam; Caressa Chen; Wesley L McKeithan; Edward Lau; Alexa Wnorowski; George McMullen; Matthew Greenhaw; Jaecheol Lee; Angelos Oikonomopoulos; Soah Lee; Huaxiao Yang; Mark Mercola; Matthew Wheeler; Euan A Ashley; Fan Yang; Ioannis Karakikes; Joseph C Wu Journal: Circulation Date: 2019-02-05 Impact factor: 29.690
Authors: Bramasta Nugraha; Michele F Buono; Lisa von Boehmer; Simon P Hoerstrup; Maximilian Y Emmert Journal: Clin Pharmacol Ther Date: 2018-12-21 Impact factor: 6.875
Authors: Wesley L McKeithan; Alex Savchenko; Michael S Yu; Fabio Cerignoli; Arne A N Bruyneel; Jeffery H Price; Alexandre R Colas; Evan W Miller; John R Cashman; Mark Mercola Journal: Front Physiol Date: 2017-10-11 Impact factor: 4.566
Authors: Erica M Fatica; Gina A DeLeonibus; Alisha House; Jillian V Kodger; Ryan W Pearce; Rohan R Shah; Liraz Levi; Yana Sandlers Journal: Metabolites Date: 2019-12-17