期刊
DEVELOPMENT
卷 142, 期 18, 页码 3188-3197出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.123034
关键词
hEPI-NCSC; Neural crest; Schwann cell; Peripheral nerve; SOX10; KROX20; Protein zero; EPI-NCSCs
资金
- Medical Research Council UK [G0802547]
- Innovative Medicines Initiative Joint Undertaking [115439]
- European Union
- European Federation of Pharmaceutical Industries and Associations (EFPIA) companies
- MRC [G0802547] Funding Source: UKRI
- Medical Research Council [G0802547] Funding Source: researchfish
We show that highly pure populations of human Schwann cells can be derived rapidly and in a straightforward way, without the need for genetic manipulation, from human epidermal neural crest stem cells [hEPI-NCSC(s)] present in the bulge of hair follicles. These human Schwann cells promise to be a useful tool for cell-based therapies, disease modelling and drug discovery. Schwann cells are glia that support axons of peripheral nerves and are direct descendants of the embryonic neural crest. Peripheral nerves are damaged in various conditions, including through trauma or tumour-related surgery, and Schwann cells are required for their repair and regeneration. Schwann cells also promise to be useful for treating spinal cord injuries. Ex vivo expansion of hEPI-NCSC isolated from hair bulge explants, manipulating the WNT, sonic hedgehog and TGF beta signalling pathways, and exposure of the cells to pertinent growth factors led to the expression of the Schwann cell markers SOX10, KROX20 (EGR2), p75NTR (NGFR), MBP and S100B by day 4 in virtually all cells, and maturation was completed by 2 weeks of differentiation. Gene expression profiling demonstrated expression of transcripts for neurotrophic and angiogenic factors, as well as JUN, all of which are essential for nerve regeneration. Co-culture of hEPI-NCSC-derived human Schwann cells with rodent dorsal root ganglia showed interaction of the Schwann cells with axons, providing evidence of Schwann cell functionality. We conclude that hEPI-NCSCs are a biologically relevant source for generating large and highly pure populations of human Schwann cells.
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