Cardiac Bio-Nanonetwork: Extracellular Vesicles Release Modeling for Engineered Stem Cell-Derived Cardiomyocyte

Abstract

Molecular communication (MC) is an interdisciplinary research area with vast potential in biomedical applications, including delivery of drugs or other therapeutic molecules in cardiovascular and other pathological conditions. The bio-molecules release modeling in MC systems is an open problem in designing the physical and chemical signal interaction level in the MC hierarchy. This also includes the release of extracellular vesicles (EVs), which are shed by all cell types and serve as nano-vehicles carrying various molecular cargo. In this paper, we propose to use engineered human induced pluripotent stem cells differentiated into atrial cardiomyocytes (ACMs) in a cardiac bio-nanonetwork and mathematically model the release of therapeutic EVs under voltage clamp. We study the stochastic nature of the proposed targeted drug delivery system by modeling the release process from engineered ACMs as a Poisson process. We model the engineered ACMs as an EV emission model, where the input signal is the voltage clamp to modulate the EV release, and the output signal is the rate of released EVs. We also study the non-linearity of the proposed EV emission system by a non-linear autoregressive exogenous model. Future drug delivery applications for cardiovascular diseases can utilize the proposed EV release modeling for engineered ACMs.