Revealing nervous and cardiac system interactions by iPSC-Based platforms

Cardiac function is regulated by the autonomic nervous system. In exchange, the sensorial information from the heart is relayed to the brain via sensory neurons as a crucial modulatory feedback mechanism. Cardiovascular and neurological diseases constitute the majority of deaths globally. The high morbidity associated with cardiac and neurological disorders is mostly due to the limited number of targeted therapeutics. Moreover, many new drug candidates are withdrawn from clinical use due to cardiotoxicity or neurotoxicity. Previously, experimental animal models, biopsy materials, or immortalized cell lines were the basis of disease studies and drug screens. However, the differences between these models and human physiology particularly in neural and cardiac functions resulted in limited clinical success. To overcome the complications related to the organism mismatch and cell source, human induced pluripotent stem cells (hiPSCs) provide ways to investigate molecular mechanisms in embryonic, adult, and diseased states. hiPSC-derived cardiac cells and various neuron subtypes could replicate complex interactions in the physiologically relevant organoids or multiorgan microdevices. Using these novel technical developments, recent models of neuronal regulation of heart tissue started to provide unique insights in systemic interactions and molecular basis to develop more precise therapeutic approaches. In this chapter, a brief historical perspective and recent advances in iPSC-based models of cardiac and nervous system interactions are reviewed.