TY - JOUR
T1 - Modeling of Modulated Exosome Release from Differentiated Induced Neural Stem Cells for Targeted Drug Delivery
AU - Veletic, Mladen
AU - Barros, Michael Taynnan
AU - Arjmandi, Hamidreza
AU - Balasubramaniam, Sasitharan
AU - Balasingham, Ilangko
N1 - Funding Information:
Manuscript received February 8, 2020; revised April 23, 2020 and April 27, 2020; accepted April 28, 2020. Date of publication May 6, 2020; date of current version July 1, 2020. This work was supported in part by the EU (EU-H2020-FETOpen GLADIATOR—Next-generation Theranostics of Brain Pathologies with Autonomous Externally Controllable Nanonetworks: A Trans-disciplinary Approach with Bio-nanodevice Interfaces) under Grant #828837 and in part by the Research Council of Norway (RCN:WINNOW—Wireless In-body Sensor and Actuator Networks) under Grant #270957. (Corresponding author: Mladen Veletić.) Mladen Veletić is with the Intervention Centre, Oslo University Hospital (OUS), 0372 Oslo, Norway, and also with the Faculty of Electrical Engineering, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina (e-mail: [email protected]).
Publisher Copyright:
© 2002-2011 IEEE.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Brain
KW - drug delivery systems
KW - exosomes
KW - glioblastoma
KW - molecular communication
KW - stem cells
UR - http://www.scopus.com/inward/record.url?scp=85084215149&partnerID=8YFLogxK
U2 - 10.1109/TNB.2020.2991794
DO - 10.1109/TNB.2020.2991794
M3 - Article
C2 - 32365033
AN - SCOPUS:85084215149
SN - 1536-1241
VL - 19
SP - 357
EP - 367
JO - IEEE Transactions on Nanobioscience
JF - IEEE Transactions on Nanobioscience
IS - 3
M1 - 9083952
ER -
