Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 μs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 μs and 5 μs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.

α-synuclein is an increasingly prominent player in the pathology of a variety of neurodegenerative conditions. Parkinson’s disease (PD) is a neurodegenerative disorder that affects mainly the dopaminergic neurons in the substantia nigra of the brain. Typical of PD pathology is the finding of protein aggregations termed ‘Lewy bodies’ in the brain regions affected. α-synuclein is implicated in many disease states including dementia with Lewy bodies and Alzheimer’s disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the α-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes α-synuclein. A variety of model systems have been employed to study α-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of α-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient's genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focus on the current knowledge about α-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.

Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly caused by hyper excitation of specific areas in the atrium resulting in dyssynchronous atrial contractions, leading to severe consequences such as heart failure and stroke. Current therapeutics aim to target this condition through both pharmacological and non-pharmacological approaches. To test and validate any of these treatments, an appropriate preclinical model must be carefully chosen to refine and optimise the therapy features to correctly reverse this condition. A broad range of preclinical models have been developed over the years, with specific features and advantages to closely mimic the pathophysiology of atrial fibrillation. In this review, currently available models are described, from traditional animal models and in vitro cell cultures to state-of-the-art organoids and organs-on-a-chip. The advantages, applications and limitations of each model are discussed, providing the information to select the appropriate model for each research application.