Thermal control of engineered induced pluripotent stem cells via focused ultrasound

Abstract

Sonogenetics has drawn significant interest from the neuromodulation community since its inception, due to its non-invasive and targeted modulation of neurons. Simultaneously, stem cell therapy presents a promising avenue for addressing neurodegenerative disorders like Parkinson's disease. Central to the field of stem cell therapy is cell fate engineering, which leverages induced pluripotent stem cells (iPSCs) to generate therapeutically relevant cell types capable of combating neurodegeneration. Although the inducible overexpression of transcription factors (TFs) through drug administration can convert neural progenitors into mature neurons, its application in the brain is hindered by systemic side effects and the challenges posed by the blood-brain barrier, impeding efficient drug delivery. In this context, we present our recent in vitro work on a sonogenetics-enabled system that allows for spatial and temporal control of TFs, enabling the direct programming of human stem cells. By incorporating heat shock promotors, we have developed a method to thermally regulate engineered iPSCs using focused ultrasound, thereby directing their differentiation into dopaminergic neurons. Our findings suggest that this approach holds promise as a potential therapeutic strategy for treating Parkinson's disease.