Idiopathic Parkinson's disease patient-derived induced pluripotent stem cells function as midbrain dopaminergic neurons in rodent brains

J Neurosci Res. 2017 Sep;95(9):1829-1837. doi: 10.1002/jnr.24014. Epub 2017 Feb 24.

Abstract

Patient-specific induced pluripotent stem cells (iPSCs) are a promising source for cell transplantation therapy. In Parkinson's disease (PD) patients, however, their vulnerability and the transmission of pathological α-Synuclein are possible drawbacks that may prevent PD-specific iPSCs (PDiPSCs) from being used in clinical settings. In this study, we generated iPSCs from idiopathic PD patients and found that there was no significant vulnerability between dopaminergic (DA) neurons generated from healthy individuals and idiopathic PD patients. PDiPSC-derived DA neurons survived and functioned in the brains of PD model rats. In addition, in the brains of α-Synuclein transgenic mice, PDiPSC-derived DA neurons did not cause pathological α-Synuclein accumulation in the host brain or in the grafts. These results suggested that iPSCs derived from idiopathic PD patients are feasible as donor cells for autologous transplantation to treat PD. © 2017 Wiley Periodicals, Inc.

Keywords: Parkinson's disease; dopaminergic neurons; rat brain; transgenic mice; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Dopaminergic Neurons / cytology*
  • Female
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells / transplantation*
  • Male
  • Mesencephalon / cytology
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Parkinson Disease*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / methods