Concise Review: Drug Discovery in the Age of the Induced Pluripotent Stem Cell

Abstract

For decades, the paradigm of drug discovery and development has relied on immortalized cell lines, animal models of human disease, and clinical trials. With the discovery of induced pluripotent stem cell (iPSC) technology in 2007, a new human in vitro drug testing platform has potentially augmented this set of tools by providing additional ways to screen compounds for safety and efficacy. The growing number of human disease models made with patient-specific iPSCs has made it possible to conduct research on a wide range of disorders, including rare diseases and those with multifactorial origin, as well as to simulate drug effects on difficult-to-obtain tissues such as brain and cardiac muscle. Toxicity and teratogenicity assays developed with iPSC-derived cells can also provide an additional layer of safety before advancing drugs to clinical trials. The incorporation of iPSC technology into drug therapy development holds promise as a more powerful and nuanced approach to personalized medicine.

Human pluripotent stem-cell-derived cardiomyocytes in cardiovascular drug discovery and development

“…However it Stem-cell-derived cardiomyocytes is hard to ignore the marked differences in physiology between humans and animals. This has contributed greatly to the significant lack of conformity between current testing procedures and human outcomes, especially in the evaluation of toxicity and drug dosing [5]. Alarmingly a survey of pharmaceutical companies displayed that data obtained from rodents failed to predict 60% of human toxicity incidents held accountable for 30% of drug failures in clinical trials.…”

“…Since the concept of iPSC technology was first explored, approximately seventy hiPSC models of rare and complex human diseases have been published and current momentum is further increasing this [5]. The appeal of reprogramming somatic cells to a pluripotent state with the ability to differentiate into any cell type found within the human body was greeted with enormous optimism.…”

“…The genetic diversity offers a magnitude of distinct disease phenotypes, some of which may not be possible in animal models. This will facilitate a powerful insight into mechanisms behind an array of diseases allowing for the effective study in the view of developing diagnostic or therapeutic applications [5].…”

“…One highly promising offering is the development of a more physiologically relevant in vitro model, which harbours the potential for enhancing the likelihood for successful translation of preclinical discoveries into clinical treatment. By using an improved testing platform the incorporation of the complexity of the clinical human disease phenotype can be achieved, addressing and potentially overcoming the limitations of current testing platforms [5].…”

Animal use for science in Europe

“…Most importantly, animal-free basic biomedical research possibilities also have been transformed dramatically. The most important new trends comprise the advent of human stem cell technology (Corti et al, 2015;Singh et al, 2015;Schadt et al, 2014;Giri and Bader, 2015;Kim et al, 2014;Lancaster and Knoblich, 2014;Karakikes et al, 2014;Inoue et al, 2014;Ko and Gelb, 2014), the option to introduce defined genetic changes into such cells (Li et al, 2014), and the construction of microphysiological systems based on human cells (Materne et al, 2015;Fabre et al, 2014;Sung et al, 2014;Hartman et al, 2014;Marx et al, 2012;Andersen et al, 2014;Hartung, 2014).…”