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Simple and Animal-Free Platform for Neural Conversion of Human Pluripotent Stem Cells

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Review of “Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal-Free Conditions” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The neural differentiation of human pluripotent stem cells currently relies on inefficient embryoid body formation, complex techniques, multiple animal components, and expensive supplements. Avoiding all these factors may promote the clinical application of human pluripotent stem cell-derived neural stem/progenitor cells and their derivatives to the treatment of various diseases and disorders.

In a new STEM CELLS Translational Medicine study [1], researchers from the laboratory of Slaven Erceg (CIPF, Valencia, Spain) have optimized culture components and employed human extracellular matrix to improve a previously developed neural differentiation technique [2]. Lukovic et al now hope that their simple and animal-free platform for the efficient neural conversion of human pluripotent stem cells will boost the clinical application of highly utile neural cells.

So just how effective and flexible is this new platform?

  • Differentiation of hESCs/hiPSCs to neural progenitor cells (NPCs) employed human foreskin fibroblast feeder layer and Insulin-transferrin-sodium selenite (ITS) medium for 7 days
    • Developing neural tube-like rosettes with lumens transferred to human matrix (CellStart) and maintained in ITS medium for a further 7 days
    • Final NPC differentiation (21 days total) employed human laminin/polyornithine matrix and ITS medium
    • 95% of NPCs expressed neural markers, but not pluripotency markers or markers of the mesodermal/endodermal lineage
  • Differentiation to mature, electrically active neurons employed neural proliferation medium (NPM) 
    • Generated 80-85% electrophysiologically functional and synaptically connected neurons
    • NPCs also held the potential to differentiate into spinal motoneurons, mature oligodendrocytes, and dopaminergic neurons
  • NPCs grown in long-term culture expanded well, maintained stability, and could be frozen and thawed without detectable alterations in proliferation or differentiation properties
  • Transplantation of NPCs into the postnatal mouse central nervous system suggested that cells survived and grafted, but did not form teratomas

The animal-free nature of the growth medium/matrix employed, as well as the simplicity, cheapness, and effectiveness, make this neural cell-generating platform apt for clinical application, with clear advantages over other related techniques that use expensive supplements, animal-derived products, and embryoid bodies. Furthermore, the patient- and disease-specific nature of the neural cells generated may also make them an invaluable tool in disease modeling and pharmacological screening.

Keep the Stem Cells Portal bookmarked to see the future success of this simple and animal-free platform for neural conversion of human pluripotent stem cells.

References

  1. Lukovic D, Diez Lloret A, Stojkovic P, et al. Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal-Free Conditions. STEM CELLS Translational Medicine 2017;6:1217-1226.
  2. Erceg S, Lainez S, Ronaghi M, et al. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions. PLoS One 2008;3:e2122.