Mifepristone-inducible caspase-1 expression in mouse embryonic stem cells eliminates tumor formation but spares differentiated cells in vitro and in vivo

Yi Wang, Dehua Yang, Lin Song, Ting Li, Juan Yang, Xiaojie Zhang, Weidong Le

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Embryonic stem cell (ESC)-based therapy is a promising treatment for neurodegenerative diseases. But there is always a risk of tumor formation that is due to contamination of undifferentiated ESCs. To reduce the risk and improve ESC-based therapy, we have established a novel strategy by which we can selectively eliminate tumor cells derived from undifferentiated ESCs but spare differentiated cells. In this study, we generated a caspase-1-ESC line transfected with a mifepristone-regulated caspase-1 expression system. Mifepristone induced caspase-1 overexpression both in differentiated and undifferentiated caspase-1-ESCs. All the undifferentiated caspase-1-ESCs were induced to death after mifepristone treatment. Tumors derived from undifferentiated caspase-1-ESCs were eliminated following 3 weeks of mifepristone treatment in vivo. However, differentiated caspase-1-ESCs survived well under the condition of mife-pristone- induced caspase-1 overexpression. To examine in vivo the impact of mifepristone-induced caspase-1 activation on grafted cells, we transplanted wild-type ESCs or caspase- 1-ESCs into nude mice brains. After 8 weeks of mifepristone treatment, we could not detect any tumor cells in the caspase- 1-ESC grafts in the brains of mice. However, we found that donor dopamine neurons survived in the recipient brains. These data demonstrate that mifepristone-induced caspase-1 overexpression in ESCs can eliminate the potential tumor formation meanwhile spares the differentiated cells in the host brains. These results suggest that this novel ESC-based therapy can be used in Parkinson's disease and other related disorders without the risk of tumor formation.

Original languageEnglish (US)
Pages (from-to)169-179
Number of pages11
Issue number2
StatePublished - Feb 2012


  • Caspase
  • Embryonic stem cell
  • Neural differentiation
  • Transplantation
  • Tumor cell purging

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine


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