Biophysical approaches for modulating neural differentiation

Abstract

Neural differentiation of stem cells is central to regenerative strategies towards neurodegenerative diseases. The vast majority of literature shows chemical, biochem ical and genetic approaches to control and utilize intrinsic or extrinsic stem cells for neural regeneration. However, biophysical factors are also able to regulate stem cell fate with some added advantages. They can be administered to organisms completely non-invasively or used as an integral part of in vitro models. Effects of substrate stiff ness and electromagnetic fields on neural differentiation are reported in the literature but common for both is a lack of understanding how these biophysical factors interact with cells. The overarching goal of this thesis is to reveal new clues about the effect mechanism of these factors on neural differentiation. Towards this end, three differ ent in vitro neural differentiation models were used in a mechanistic investigation. In the first segment, the results highlight a novel, integrin-independent and biomimetic mechanosensitivity of human neuroblastoma differentiation, along with new caveats attached to using this in vitro biological model. The following segments on electro magnetic fields reveal an unprecedented finding where zinc ions rush into the cells during chronic exposure to 50 Hz electromagnetic field and facilitate other, previously known effects of electromagnetic fields. Moreover, two different ion channels were asso ciated with these effects, for the first time in the literature. Overall, the output of this thesis identifies three new key players for sensing biophysical factors during neural dif ferentiation that will substantially contribute to future efforts towards their utilization in neural regeneration research.|Keywords : Mechanotransduction, extremely low frequency electromagnetic fields, neural differentiation, calcium influx, NMDA receptor, zinc, TRP channels.