4.5 Article

Modeling of Modulated Exosome Release From Differentiated Induced Neural Stem Cells for Targeted Drug Delivery

Journal

IEEE TRANSACTIONS ON NANOBIOSCIENCE
Volume 19, Issue 3, Pages 357-367

Publisher

IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TNB.2020.2991794

Keywords

Neurons; Calcium; Mathematical model; Stem cells; Cancer; Nanobioscience; Extracellular; Brain; drug delivery systems; exosomes; glioblastoma; molecular communication; stem cells

Funding

  1. EU (EU-H2020-FETOpen GLADIATOR-Next-generation Theranostics of Brain Pathologies with Autonomous Externally Controllable Nanonetworks: A Trans-disciplinary Approach with Bio-nanodevice Interfaces) [828837]
  2. Research Council of Norway (RCN:WINNOW-Wireless In-body Sensor and Actuator Networks) [270957]

Ask authors/readers for more resources

A novel implantable and externally controllable stem-cell-based platform for the treatment of Glioblastoma brain cancer has been proposed to bring hope to patients who suffer from this devastating cancer type. Induced Neural Stem Cells (iNSCs), known to have potent therapeutic effects through exosomes-based molecular communication, play a pivotal role in this platform. Transplanted iNSCs demonstrate long-term survival and differentiation into neurons and glia which then fully functionally integrate with the existing neural network. Recent studies have shown that specific types of calcium channels in differentiated neurons and astrocytes are inhibited or activated upon cell depolarization leading to the increased intracellular calcium concentration levels which, in turn, interact with mobilization of multivesicular bodies and exosomal release. In order to provide a platform towards treating brain cancer with the optimum therapy dosage, we propose mathematical models to compute the therapeutic exosomal release rate that is modulated by cell stimulation patterns applied from the external wearable device. This study serves as an initial and required step in the evaluation of controlled exosomal secretion and release via induced stimulation with electromagnetic, optical and/or ultrasonic waves.

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