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.

中文翻译：

---

从分化诱导的神经干细胞中定向释放药物的调节性外泌体释放模型。

已经提出了用于治疗胶质母细胞瘤脑癌的新颖的可植入且可外部控制的基于干细胞的平台，以给患有这种毁灭性癌症类型的患者带来希望。诱导的神经干细胞（iNSC），已知通过基于外泌体的分子交流具有有效的治疗作用，在该平台中起着关键作用。移植的iNSC可以长期存活并分化为神经元和神经胶质，然后与现有的神经网络完全功能整合。最近的研究表明，在细胞去极化时，分化的神经元和星形胶质细胞中特定类型的钙通道被抑制或激活，导致细胞内钙浓度水平升高，进而与多囊体动员和胞外释放相互作用。为了提供一种以最佳治疗剂量治疗脑癌的平台，我们提出了数学模型来计算治疗性外泌体释放速率，该释放速率由从外部可穿戴设备施加的细胞刺激模式调节。这项研究是评估通过电磁波，光波和/或超声波诱导的刺激来控制外泌体分泌和释放的第一步和必需步骤。