Noninvasive Optogenetics Realized by iPSC-Derived Tentacled Carrier in Alzheimer's Disease Treatment.

Abstract

Neural-activated optogenetics technique contributing to the "restart" of degenerative neurons offers hope for the treatment of several neurodegenerative diseases. However, the limitations of persistent invasiveness and inadequate repair of the pathological environment strongly hinder its further application. Here, a concept of differentiating stem cells is proposed to produce functional materials to enhance the therapeutic applicability of optogenetics. Induced pluripotent stem cells (iPSCs) are differentiated to generate the "tentacled" stem cells TenSCs. Their "tentacled" vesicles TenSCev, upon inheriting the biological functions of the parent cell, will possess both neural targeting capacity and pathological environment repair ability. Hence, TenSCev are utilized as functional carrier to deliver optogenetics elements for completely non-traumatic and controllable neuron activation, while also facilitating the comprehensive restoration of the pathological environment, thus effectively halted disease progression and significantly improved cognitive function in Alzheimer's disease or aged mice. Further, the concept of generating specialized biomaterials from differentiated stem cells as functional carriers holds the potential to broaden the applicability of various neuroregulatory techniques in the treatment of neurological disorders.