Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

Abstract

Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.

Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics

“…Although experimental challenges still need to be overcome, dissecting mechanisms along the heart-brain axis has become more achievable with the introduction of innovative methods, imaging ( Bruegmann et al., 2010 ; Prando et al., 2018 ; Sigalas et al., 2020 ; Vaseghi et al., 2012 ), and tissue engineering techniques ( Burton et al., 2015 ; Klimas et al., 2016 ). In summary, we investigated the effect of sympathetic innervation on the activation dynamics of a cardiac cell monolayer innervated in vitro by co-culture with stellate ganglia neurons.…”

“…Although dye-free imaging offers long-term, non-contact precision control of wave properties that pharmacological and electrical methods lack, the interpretation of complex spiral wave patterns may be hindered by similarities in the optical signals from excitation and relaxation waves ( Sigalas et al., 2020 ). Low-density neuron co-culture dishes offered interesting observations that may be of clinical relevance; however, the technical challenges of ensuring low numbers of neurons that are present and functional in these co-cultures currently highlight a limitation of this approach.…”

Lysosomal signalling pathways influence heart rhythm, and regulate atrial function

“…NRAMs were isolated using a modified protocol from [67] and [68]. Hearts were dissected from 3-day-old Sprague Dawley rat pups, culled by cervical dislocation followed by exsanguination.…”

Lysosomal signalling pathways influence heart rhythm, and regulate atrial function

“…NRAMs were isolated using a modified protocol from [67] and [68]. Hearts were dissected from 3-dayold Sprague Dawley rat pups, culled by cervical dislocation followed by exsanguination.…”