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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Daisuke Doi
  • Bumpei Samata
  • Mitsuko Katsukawa
  • Tetsuhiro Kikuchi
  • Asuka Morizane
  • Yuichi Ono
  • Kiyotoshi Sekiguchi
  • Masato Nakagawa
  • Malin Parmar
  • Jun Takahashi
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)337-350
JournalStem Cell Reports
Volume2
Issue number3
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Developmental Neurobiology (013210001), Neuronal Survival (013212041)