Research Projects

Background: Cardiovascular diseases (CVDs) are a primary cause of death worldwide, including India. The brain-heart axis controls cardiovascular function, and aberrant sympathetic nervous system activity can lead to heart failure. Current research is exacerbated by a lack of appropriate model systems for studying molecular interactions between neurones and the circulatory system. Further research into the neurological components of CVDs may uncover disease processes, enhance diagnosis, and lead to more effective treatments and drug discovery platforms. Rationale: Traditional animal models are common in cell biology for human disease research, however, they often provide inaccurate results owing to species differences in disease mechanisms and drug responses, particularly for cardio and neurotoxicity. This makes them unsuitable for precisely studying human pathophysiological conditions. While advanced 3D cell culture technologies and microfluidic platforms offer promising avenues for studying cell-to-cell interactions and tissue architecture, a comprehensive humanized in vitro model of the heart with integrated neuronal and vascular features remains elusive. This proposal aims to address this gap by utilizing novel microfluidic platforms with 3D soft gel cultures and dynamic fluidic shear stress to establish a more precise model to offer a holistic view of disease pathophysiology and significantly contributing to improved disease management strategies. Outcome: NVMyC-Chip, a ground-breaking and patentable microfluidic model featured with three interconnected channels, enabling the co-culture of fully engineered 3D cellular subtypes to accurately mimic the in vivo architecture of the innervated myocardium. This model is expected to delve deeper into the complex interactions between neurones and myocardium in a variety of pathological cardiac diseases. This model promises to provide unique mechanistic insights into both the developmental and pathological interactions of the heart. Significance: Difficulties in isolating and culturing human cardiomyocytes and neurons hinder our understanding of their biology. Animal models and non-human cells often show distinct maturation features compared to human cells, underscoring the need for a human-centric neuro-vascular-myocardium model. This proposal introduces the NVMyC-chip, a compartmentalized microfluidic device with neuronal, endothelial, and myocardium units. This chip offers spatial separation and niche control, along with compatibility for advanced 3D cultures to enhance cell function. This human-derived model will serve as a crucial tool for understanding neuroradiology pathophysiology, drug discovery, disease modelling, and toxicity screening on a human genetic background with the potential to replace animal models.

Neurocardiology, Myocardium, Innervation, Pathophysiology, Microfluidics, NVMyC-chip