Stem Cells Dev. 2015 Mar 6. [Epub ahead of print]

Advances in reprogramming based study of neurologic disorders.

Nityanandam A¹, Baldwin KK.

Abstract

The technology to convert adult human non-neural cells into neural lineages, through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer (SCNT), and direct lineage conversion or transdifferentiation has progressed tremendously in recent years. Reprogramming based approaches aimed at manipulating cellular identity have enormous potential for disease modeling, high throughput drug screening, cell therapy and personalized medicine. Human iPSC- based cellular disease models have provided proof-of-principle evidence of the validity of this system. However, several challenges remain before patient specific neurons produced by reprogramming can provide reliable insights into disease mechanisms or be applied efficiently to drug discovery and transplantation therapy. This review will first discuss limitations of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology. Specifically, we will address issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two dimensional differentiation paradigms. Second, we will assess recent progress and the future prospects of reprogramming-based neurologic disease modeling. This includes three dimensional disease modeling, advances in reprogramming technology, pre-screening of human iPSCs, creating isogenic disease models using gene editing, and in vivo reprogramming.