chemical conversion of human fibroblasts into functional schwann cells

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
nature reviews gastroenterology & hepatology 2014 Vol. 3 pp. 539-547
116
thoma2014stemchemical

Abstract

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.

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254692
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10.1016/j.stemcr.2014.07.014
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