Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation

Stem Cell Reports. 2014 Mar 6;2(3):337-50. doi: 10.1016/j.stemcr.2014.01.013. eCollection 2014 Mar 11.


Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN(+) cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN(+) cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN(+) cells in a NURR1(+) cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cell Culture Techniques
  • Cell Differentiation*
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / transplantation*
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mesencephalon / cytology
  • Mesencephalon / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Rats
  • Serine Endopeptidases / metabolism
  • Time Factors


  • CORIN protein, human
  • Serine Endopeptidases