Stem Cell Reports (Oct 2014)

Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

  • Eva C. Thoma,
  • Claudia Merkl,
  • Tobias Heckel,
  • Rachel Haab,
  • Frederic Knoflach,
  • Corinne Nowaczyk,
  • Nicholas Flint,
  • Ravi Jagasia,
  • Sannah Jensen Zoffmann,
  • Hoa Hue Truong,
  • Pascal Petitjean,
  • Sebastian Jessberger,
  • Martin Graf,
  • Roberto Iacone

DOI
https://doi.org/10.1016/j.stemcr.2014.07.014
Journal volume & issue
Vol. 3, no. 4
pp. 539 – 547

Abstract

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Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs) expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes.