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Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells
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Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells

Published on: May 22, 2014

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PSA-NCAM-negative neural crest cells emerging during neural induction of pluripotent stem cells cause mesodermal

Dongjin R Lee1, Jeong-Eun Yoo1, Jae Souk Lee1

  • 1Department of Physiology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.

Stem Cell Reports
|May 5, 2015
PubMed

Insights

Tumorigenic potential in human pluripotent stem cell (hPSC)-derived neural precursor cells (NPCs) is linked to polysialic acid-neural cell adhesion molecule (PSA-NCAM) negative cells, identified as neural crest stem cells (NCSCs). Removing these PSA-NCAM(-) NCSCs prevents tumor formation in transplantation models.

Area of Science:

  • Stem cell biology
  • Neuroscience
  • Cancer research

Background:

  • Tumorigenicity of human pluripotent stem cells (hPSCs) is a major hurdle for clinical applications.
  • hPSC-derived neural precursor cells (NPCs) can induce tumors, even without detectable undifferentiated pluripotent cells.

Purpose of the Study:

  • Identify the specific cell population responsible for tumor formation in hPSC-derived NPCs.
  • Determine if targeting this population can prevent tumorigenicity.

Main Methods:

  • Flow cytometry to isolate polysialic acid-neural cell adhesion molecule (PSA-NCAM) positive and negative cells from NPCs.
  • Molecular profiling and gene expression analysis of PSA-NCAM(-) cells.
  • In vivo transplantation studies in rat brains to assess tumorigenicity.

Main Results:

  • PSA-NCAM(-) cells, but not PSA-NCAM(+) cells, induced tumors upon transplantation.
  • PSA-NCAM(-) cells were identified as multipotent neural crest stem cells (NCSCs) capable of ectodermal and mesodermal differentiation.
  • Co-transplantation of PSA-NCAM(-) cells with PSA-NCAM(+) cells proportionally increased mesodermal tumor formation and unwanted cell types.

Conclusions:

  • Neural crest stem cells (NCSCs) are the source of tumorigenicity in hPSC-derived NPCs.
  • Eliminating PSA-NCAM(-) NCSCs is a viable strategy to prevent tumor formation after transplantation of hPSC-derived NPCs.

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