Human induced pluripotent stem cells and neurodegenerative disease

Abstract

Purpose of review The lack of effective treatments for various neurodegenerative disorders has placed huge burdens on society. We review the current status application of pluripotent stem cells (iPSCs) technology for the cellular therapy, drug screening and in vitro modeling of neurodegenerative diseases. Recent findings Disease specific iPSCs were derived from patients of several major neurodegenerative diseases, including Parkison' disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Differentiation of the SMA-iPSCs into neurons showed the recapitulation of the in vivo phenotypes, allowing us the future use of drug screening. The murine model of Parkinson's transplanted with human iPSCs showed the functional recovery, showing the potential of iPSC as cell therapy. Direct conversion to neurons was succeeded from skin fibroblasts of Alzheimer's patients. Summary We summarize the recent progress in using iPSCs for neurodegenerative diseases, and provide a future perspective in this field.

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

“…The most successful examples of this strategy have used diseases that have strong genetic components and affect a highly defined cell type leading to a characteristic difference to an unaffected cell, e.g. for diseases with a known molecular mechanism, such as in spinal muscular atrophy, HutchinsonGilford Progeria syndrome, familial Parkinson's disease or Down syndrome (Ebben et al 2011;Malpass 2011;Jung et al 2012;Shi et al 2012). and PSEN2 (N141I), and characterized their subsequent differentiation into neurons (Yagi et al 2011).…”

Proneural Transcription Factor Atoh1 Drives Highly Efficient Differentiation of Human Pluripotent Stem Cells Into Dopaminergic Neurons

“…Human PSCs, especially patient-derived iPSCs, hold enormous promise for various applications in regenerative medicine, including disease modeling, drug development, and cell replacement therapy [1][2][3]. In order to fully use these patient-specific iPSCs in regenerative medicine, highly efficient differentiation strategies are required to drive iPSCs into desired lineages and generate functional cell progenies, such as various subtypes of neurons.…”

The Pharmacology of Regenerative Medicine

“…Examples of specific conditions for which patient-specific iPS cells have been obtained and differentiated into disease-relevant cell types include Parkinson's disease (Byers et al, 2012;Jang et al, 2012) and other neurodegenerative disorders Jung et al, 2012), Wilson's disease (Yi et al, 2012), lysosomal storage disorders (Huang et al, 2012b), and diabetes (Fujikura et al, 2012).…”