Three reasons why iPSC-derived atrial cardiomyocytes are poised to accelerate atrial fibrillation research
Atrial fibrillation is estimated to affect around 6 million people in Europe, making it the most common arrhythmia observed in the clinic. The irregular heartbeat and disturbed electrical activity experienced by atrial fibrillation patients is commonly treated by surgical interventions such as pacemakers or the ablation of diseased tissue, or with non-selective class IC (Nav) and III (Kv) ion channel anti-arrhythmic drugs. However, these approaches can have serious side-effects, so extensive research has been devoted to better understand the cellular mechanisms behind the disease to develop safer and more effective treatments.
Atrial fibrillation is the most common arrhythmia observed in the clinic, affecting 6 million patients in Europe and accounting for 30% of strokes. The prevalence of atrial fibrillation continues to grow due to an aging population and is expected to double over the next 50 years. Given the need to develop safer and more effective anti-arrhythmic therapeutics, considerable efforts have been made to understand the cellular mechanisms of the disease and translate this knowledge into innovative treatments.
Cardiovascular diseases (CVD) include coronary heart disease, stroke, myocardial infarction and heart failure. They are the leading cause of mortality globally, with CVD accounting for 31% of deaths worldwide in 2015. Within the UK alone 27.4% of male deaths and 25.2% of female deaths in 2015 were due to CVD.
Traditionally, there have been difficulties in obtaining and culturing human cardiac cells of a high quality due to a scarcity of healthy donor material, culture issues associated with the non-dividing state of terminally differentiated cardiomyocytes. The development of human embryonic stem cell technology allowed major advancements to be made as protocols were developed to differentiate cardiomyocytes from a replenishable pluripotent source. A huge issue with the use of human embryonic stem cell-derived cells was the controversial ethical issues and strict regulations regarding their use. This meant that Yamanaka's breakthrough when his group produced the Nobel Prize winning technology in the form of induced pluripotent stem cells had a gargantuan impact on the study of human cardiac cells.
Drug toxicity is a significant cause of clinical failure, accounting for approximately one third of all pipeline attrition. This has driven huge interest across the pharmaceutical industry to understand drug toxicity early within the drug development pipeline. The aim of this is to de-risk drug candidates from a safety perspective before they enter the clinic, as well as reducing the substantial costs associated with drug development.
Using hiPSC-Derived Renal Proximal Tubular Cells in vitro assays to advance disease research and drug development
The rising numbers of kidney patients and a shortage of transplantable organs is a global health issue with high economic costs. Previous disease research and drug development has traditionally used animal models, but these fail to recapitulate human renal cellular function and so limit our ability to elucidate disease mechanisms and therapeutic targets.
Kidneys play a key role in removing waste and toxins from the body, as well as having essential endocrinological and homeostatic functions. If certain pharmaceuticals are abused, administered incorrectly or taken regularly, they can induce toxicity in the kidneys (nephrotoxicity). This can result in impaired renal function, and even death in the most severe cases. For example, nephrotoxic drugs (NDs) are responsible for 19-25% of acute kidney injury in critically ill patients.
The body’s immune system is our first line of defence against foreign substances, protecting us against infection and disease. It consists of a complex network of organs and cells that work to recognize and destroy these harmful substances, containing them at the site of infection. Macrophages play a crucial role in this; engulfing and destroying anything dangerous via phagocytosis.