Modeling Neurological Diseases with Induced Pluripotent Stem Cells

Abstract

Induced pluripotent stem cells (iPSCs) can differentiate into various cell types including neural cells. Because dopaminergic neurons selectively degrade in Parkinson’s disease, efficiently inducing stem cell differentiation into dopaminergic neurons is necessary for modeling Parkinson’s disease. My collaborators and I recently developed a neurosphere-based neural induction method that efficiently differentiates T cell-derived iPSCs into neural cells. We established a protocol that uses this method to efficiently and specifically induce differentiation of iPSCs into dopaminergic neurons typical of the midbrain. Furthermore, we have found that treating iPSCs with a combination of 3 inhibitors can induce a transient embryoid-like state that accelerates the expression of pathological phenotypes as the cells mature into neurons. These techniques provide a basis for efficient iPSC-based neurological disease modeling that can be used for high-throughput drug screening.