The translational potential of human induced pluripotent stem cells for clinical neurology

Abstract

The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient’s disease “in a dish.” HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies. This review will focus on the translational potential of hiPSCs in clinical neurology and the importance of integrating this approach with complementary model systems to increase the translational yield of preclinical testing for the benefit of patients. This strategy is particularly important given the expected increase in prevalence of neurodegenerative disease, which poses a major burden to global health over the coming decades.

hiPSC-Derived Neurons Provide a Robust and Physiologically Relevant In Vitro Platform to Test Botulinum Neurotoxins

“…The lack of physiologically relevant and predictive cell-based assays is one of the major obstacles ( Waring et al, 2015 ). HiPSCs hold tremendous promise for translational research in neurological diseases ( Devine and Patani, 2017 ; Silva and Haggarty, 2019 ). Such neurological diseases include, for example, Parkinson’s disease for which new compounds hold a promise as future therapeutics ( Brunetti et al, 2020 ).…”

Novel therapeutic targets for amyotrophic lateral sclerosis: ribonucleoproteins and cellular autonomy

“…An integrated approach to modeling is crucial to yield high confidence findings of translational value by reducing inherent biases of each particular model system. Human iPSCs can be predictably manipulated into becoming any human cell type without the need for artificial overexpression or knock down [182][183][184][185], whilst faithfully recapitulating human cell type-specific properties of ALS [119,[186][187][188]. A recent important example here is aberrant splicing of the microtubuleassociated stathmin-2 (STMN2) transcript caused by TDP-43 depletion in human neurons [16,17].…”

The future is now: cutting edge science and understanding toxicology

“…The promise and challenges of implementing this technology has also been covered in CBT (Devine and Patani 2017;Kim et al 2016;Driessen et al 2017). Devine and Patani provided a very useful, focused overview of the application of iPSC technology for neurological applications.…”