Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy Without Teratoma Through Selective Photosensitivity

Stem Cell Reports. 2015 Dec 8;5(6):1067-1080. doi: 10.1016/j.stemcr.2015.10.004. Epub 2015 Nov 12.

Abstract

Stem-toxic small molecules have been developed to induce selective cell death of pluripotent stem cells (PSCs) to lower the risk of teratoma formation. However, despite their high efficacies, chemical-based approaches may carry unexpected toxicities on specific differentiated cell types. Herein, we took advantage of KillerRed (KR) as a suicide gene, to selectively induce phototoxicity using visible light via the production of reactive oxygen species. PSCs in an undifferentiated state that exclusively expressed KR (KR-PSCs) were eliminated by a single exposure to visible light. This highly selective cell death in KR-PSCs was exploited to successfully inhibit teratoma formation. In particular, endothelial cells from KR-mPSCs remained fully functional in vitro and sufficient to repair ischemic injury in vivo regardless of light exposure, suggesting that a genetic approach in which KR is expressed in a tightly controlled manner would be a viable strategy to inhibit teratoma formation for future safe PSC-based therapies.

Keywords: KillerRed; ischemic injury; phototoxicity; pluripotent stem cells; teratoma; vasculogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / radiation effects
  • Cell Differentiation
  • Cell- and Tissue-Based Therapy
  • Endothelial Cells / cytology
  • Endothelial Cells / transplantation*
  • Female
  • Hindlimb / blood supply
  • Ischemia / therapy*
  • Light
  • Mice
  • Mice, Nude
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / radiation effects*
  • Reactive Oxygen Species / metabolism
  • Teratoma / prevention & control*

Substances

  • Reactive Oxygen Species