Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions

Andrzej Swistowski, Jun Peng, Qiuyue Liu, Prashant Mali, Mahendra S. Rao, Linzhao Cheng, Xianmin Zeng

Research output: Contribution to journalArticle

Abstract

Human induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells represent a promising unlimited cell source for generating patient-specific cells for biomedical research and personalized medicine. As a first step, critical to clinical applications, we attempted to develop defined culture conditions to expand and differentiate human iPSCs into functional progeny such as dopaminergic neurons for treating or modeling Parkinson's disease (PD). We used a completely defined (xeno-free) system that we previously developed for efficient generation of authentic dopaminergic neurons from human embryonic stem cells (hESCs), and applied it to iPSCs. First, we adapted two human iPSC lines derived from different somatic cell types for the defined expansion medium and showed that the iPSCs grew similarly as hESCs in the same medium regarding pluripotency and genomic stability. Second, by using these two independent adapted iPSC lines, we showed that the process of differentiation into committed neural stem cells (NSCs) and subsequently into dopaminergic neurons was also similar to hESCs. Importantly, iPSC-derived dopaminergic neurons were functional as they survived and improved behavioral deficits in 6-hydroxydopamine-leasioned rats after transplantation. In addition, iPSC-derived NSCs and neurons could be efficiently transduced by a baculoviral vector delivering episomal DNA for future gene function study and disease modeling using iPSCs. We also performed genome-wide microarray comparisons between iPSCs and hESCs, and we derived NSC and dopaminergic neurons. Our data revealed overall similarity and visible differences at a molecular level. Efficient generation of functional dopaminergic neurons under defined conditions will facilitate research and applications using PD patient-specific iPSCs.

Original languageEnglish (US)
Pages (from-to)1893-1904
Number of pages12
JournalStem Cells
Volume28
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Induced Pluripotent Stem Cells
Dopaminergic Neurons
Neural Stem Cells
Parkinson Disease
Cell Line
Precision Medicine
Genomic Instability
Oxidopamine
Biomedical Research
Transplantation
Genome

Keywords

  • Dopaminergic neuron
  • Human ESC
  • Human iPSC
  • Neural stem cell

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. / Swistowski, Andrzej; Peng, Jun; Liu, Qiuyue; Mali, Prashant; Rao, Mahendra S.; Cheng, Linzhao; Zeng, Xianmin.

In: Stem Cells, Vol. 28, No. 10, 10.2010, p. 1893-1904.

Research output: Contribution to journalArticle

Swistowski, Andrzej ; Peng, Jun ; Liu, Qiuyue ; Mali, Prashant ; Rao, Mahendra S. ; Cheng, Linzhao ; Zeng, Xianmin. / Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. In: Stem Cells. 2010 ; Vol. 28, No. 10. pp. 1893-1904.
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