Parkinson's Disease Patient-derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Mar 10

PMID 19269371

Citations 661

Authors

Frank Soldner

Dirk Hockemeyer

Caroline Beard

Qing Gao

George W Bell

Elizabeth G Cook

Gunnar Hargus

Alexandra Blak

Oliver Cooper

Maisam Mitalipova

Ole Isacson

Rudolf Jaenisch

Affiliations

Soon will be listed here.

Abstract

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients represent a powerful tool for biomedical research and may provide a source for replacement therapies. However, the use of viruses encoding the reprogramming factors represents a major limitation of the current technology since even low vector expression may alter the differentiation potential of the iPSCs or induce malignant transformation. Here, we show that fibroblasts from five patients with idiopathic Parkinson's disease can be efficiently reprogrammed and subsequently differentiated into dopaminergic neurons. Moreover, we derived hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Factor-free hiPSCs maintain a pluripotent state and show a global gene expression profile, more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.

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