The Progress of Induced Pluripotent Stem Cells as Models of Parkinson's Disease.

Ji-Feng Kang,Ji-Feng Guo,Bei-Sha Tang

doi:10.1155/2016/4126214

Abstract

In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson's disease (PD). Somatic cells from patients with SNCA (α-synuclein), LRRK2 (leucine-rich repeat kinase 2), PINK1 (PTEN induced putative kinase 1), Parkin mutations, and at-risk individuals carrying GBA (β-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, including α-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application.

Highlights

Induced pluripotent stem cells are similar to human embryonic stem cells in their morphology, self-renewing capacity, and differentiation potential to any cell types
Takahashi and Vodyanik generated Induced pluripotent stem cells (iPSCs) with retroviruses carrying transcription factors and oncogene c-Myc, which raise the risk of tumorigenicity and other side effects
Safer and more effective methods using nonintegrating vectors, synthetic modified mRNA, and small molecules instead of transgene integration have been attempted in many studies, which can directly activate the expression of transcription factors in iPSC generation through different ways

Summary

Introduction

Induced pluripotent stem cells (iPSCs) are similar to human embryonic stem cells in their morphology, self-renewing capacity, and differentiation potential to any cell types. In 2007, Takahashi et al and Vodyanik et al induced adult human somatic cells into iPSCs by transferring a series of specific transcript factors (Oct, Sox, Klf, c-Myc or Oct, Sox, Nanog, Lin28) [1, 2], which represented a new method to generate disease-specific pluripotent stem cells from the patients. Takahashi and Vodyanik generated iPSCs with retroviruses carrying transcription factors and oncogene c-Myc, which raise the risk of tumorigenicity and other side effects. Safer and more effective methods using nonintegrating vectors, synthetic modified mRNA, and small molecules (for SB431542, PD0325901, and Thiazovivin) instead of transgene integration have been attempted in many studies, which can directly activate the expression of transcription factors in iPSC generation through different ways. The new methods saved time and improved reprogramming efficiency and safety [3,4,5,6,7], which provided an alternative strategy for disease modeling and clinical study

Parkinson’s Disease

Potential Clinical Applications of iPSCs

Findings

Challenges and Future Directions