Abstract

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 TGFβ 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.

Highlights

  • Schwann cells are neural crest-derived glia that support axons of peripheral nerves

  • We provide a methodology for using hEPI-NCSC to generate large and highly pure populations of human Schwann cells using a straightforward strategy that avoids genetic modification and includes manipulation of pertinent signalling pathways with small molecules. hEPI-NCSC are multipotent adult stem cells that derive from the neural crest, a transient tissue in vertebrate embryos that originates from the dorsal aspect of the developing neural tube, the future spinal cord

  • Functionality of hEPI-NCSC-derived human Schwann cells in vitro we addressed the functionality of Schwann cells in vitro by determining whether hEPI-NCSC-derived Schwann cells can interact with neurites

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Summary

Introduction

Schwann cells are neural crest-derived glia that support axons of peripheral nerves. Injuries to peripheral nerves are common; they can be due to neuropathies, traumatic injury, tumour-related surgery or repetitive compression (Pfister et al, 2011; Griffin et al, 2014; Evans, 2001). Peripheral nerve injury carries a high cost to healthcare systems (Rosberg et al, 2005; Noble et al, 1998). Surgical repair for minor nerve reconstruction involves direct end-to-end.

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