Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

作者：Eva Thoma, Claudia Merkl, Tobias Heckel, Rachel Haab, Frédéric Knoflach, Corinne Nowaczyk, Nicholas A. Flint, Ravi Jagasia, Sannah Zoffmann, Hoa Truong, Pascal Petitjean, Sebastian Jessberger, Martin R. Graf, Roberto Iacone · 发表于：Stem Cell Reports · 年份：2014 · DOI：10.1016/j.stemcr.2014.07.014 · 被引用次数：74 · 研究领域：Nerve injury and regeneration、Pluripotent Stem Cells Research、Neurogenesis and neuroplasticity mechanisms

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.