IPSCs as a Platform for Disease Modeling, Drug Screening, and Personalized Therapy in Muscular Dystrophies.

Jose L Ortiz-Vitali,Radbod Darabi

doi:10.3390/cells8010020

Abstract

Induced pluripotent stem cells (iPSCs) are the foundation of modern stem cell-based regenerative medicine, especially in the case of degenerative disorders, such as muscular dystrophies (MDs). Since their introduction in 2006, many studies have used iPSCs for disease modeling and identification of involved mechanisms, drug screening, as well as gene correction studies. In the case of muscular dystrophies, these studies commenced in 2008 and continue to address important issues, such as defining the main pathologic mechanisms in different types of MDs, drug screening to improve skeletal/cardiac muscle cell survival and to slow down disease progression, and evaluation of the efficiency of different gene correction approaches, such as exon skipping, Transcription activator-like effector nucleases (TALENs), Zinc finger nucleases (ZFNs) and RNA-guided endonuclease Cas9 (CRISPR/Cas9). In the current short review, we have summarized chronological progress of these studies and their key findings along with a perspective on the future road to successful iPSC-based cell therapy for MDs and the potential hurdles in this field.

Highlights

Since 2006, and with the generation of induced pluripotent stem cells [1,2,3], the field of stem cell biology and regenerative medicine has developed a more optimistic outlook to providing personalized patient therapy using stem cells
IPSCs were derived via integrating viral vectors that delivered the key transcription factors Klf4, Oct3/4, Sox2, Lin-28, and c-Myc [1,2,3,7], but this posed a concern for downstream therapeutic use due to unforeseen insertional mutagenesis caused by viral genome integration
These advances, in conjunction with the possibility of the generation of tissue-specific cells from induced pluripotent stem cells (iPSCs) and new gene correction techniques, such as Transcription activator-like effector nucleases (TALENs) [14,15] and CRISPR/Cas9 [16,17], create great hopes for personalized stem cell therapy to become a reality for treating countless degenerative disorders

Summary

Introduction

Since 2006, and with the generation of induced pluripotent stem cells (iPSCs) [1,2,3], the field of stem cell biology and regenerative medicine has developed a more optimistic outlook to providing personalized patient therapy using stem cells. New methods were developed, such as non-integrating viral (Sendai virus) and non-viral methods (cDNA, mRNA, protein) that are much safer than the traditional method, and alleviate the risk of insertional mutagenesis [8,9,10,11,12,13] These advances, in conjunction with the possibility of the generation of tissue-specific cells from iPSCs and new gene correction techniques, such as TALENs [14,15] and CRISPR/Cas9 [16,17], create great hopes for personalized stem cell therapy to become a reality for treating countless degenerative disorders.

Methodology

Findings

Perspective for Therapeutic Application of iPSCs in Muscular Dystrophies