Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation

Stem Cells. 2006 Mar;24(3):763-71. doi: 10.1634/stemcells.2005-0137. Epub 2005 Oct 13.

Abstract

The differentiation of dopaminergic (DA) neurons from mouse embryonic stem cells (ESCs) can be efficiently induced, making these neurons a potential source for transplantation as a treatment for Parkinson's disease, a condition characterized by the gradual loss of midbrain DA neurons. One of the major persistent obstacles to the successful implementation of therapeutic ESC transplantation is the propensity of ESC-derived grafts to form tumors in vivo. To address this problem, we used fluorescence-activated cell sorting to purify mouse ESC-derived neural precursors expressing the neural precursor marker Sox1. ESC-derived, Sox1+ cells began to express neuronal cell markers and differentiated into DA neurons upon transplantation into mouse brains but did not generate tumors in this site. In contrast, Sox1- cells that expressed ESC markers frequently formed tumors in vivo. These results indicate that Sox1-based cell sorting of neural precursors prevents graft-derived tumor formation after transplantation, providing a promising strategy for cell transplantation therapy of neurodegenerative disorders.

MeSH terms

  • Animals
  • Antigens, Differentiation
  • Brain Stem Neoplasms / etiology
  • Cell Differentiation / physiology*
  • Cell Separation / instrumentation
  • Cell Separation / methods
  • DNA-Binding Proteins*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / physiology*
  • Flow Cytometry* / methods
  • High Mobility Group Proteins*
  • Humans
  • Mice
  • Neurons / cytology
  • Neurons / physiology*
  • Neurons / transplantation
  • Parkinson Disease / therapy
  • SOXB1 Transcription Factors
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Antigens, Differentiation
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • SOXB1 Transcription Factors
  • Sox1 protein, mouse