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Schwann cells are the glia or non-neuronal cells that help maintain relatively constant conditions, by providing support and protection for neurons in our central and peripheral nervous systems Image credit: Wikipedia

Skin stem cells coaxed to become Schwann cells

Scientists use a combination of small molecules to turn cells isolated from human skin into Schwann cells - the specialized cells which support nerves and play a role in nerve repair.

This new method generates large, pure populations of Schwann cells and is a promising step toward repair of peripheral nerve damage via a biologically accessible source of cells. Their research is published in the scientific journal Development.

Currently, nerve repair strategies involve taking grafts from patients to repair their damaged peripheral nerves. But this method has several disadvantages including, often causing nerve damage itself. Now, Motoharu Sakaue DVM, PhD, Department of Veterinary Medicine, Laboratory of Anatomy II, School of Veterinary Medicine, the Azabu University, Sagamihara, Japan, together with Maya Sieber-Blum, Professor of Stem Cell Sciences at the Institute of Genetic Medicine in Newcastle, the United Kingdom [UK], offer the possibility of stimulating the natural production of Schwann cells within controlled laboratory conditions.

Schwann cells are known to promote nerve repair. To make them, the researchers isolated stem cells from adult skin and coaxed them into becomming Schwann cells by exposing them to small molecules.

"We observed that the bulge, a region within hair follicles, contains skin stem cells intermixed with cells derived from the neural crest - a tissue known to give rise to Schwann cells. This observation raised the question whether these neural crest-derived cells are also stem cells and whether they could be used to generate Schwann cells.

"We then used small molecules to either enhance or inhibit pathways, active or inactive respectively, in the embryo during Schwann cell differentiation."

Sieber-Blum.

With this approach, the scientists were able to generate large and highly pure populations of human Schwann cells. The cells' morphology is characteristic of Schwann cells and expressed Schwann cell markers. Further testing revealed these Schwann cells could interact with nerves in vitro.

"The next step is to determine in animal models with peripheral nerve injury, whether grafts of these Schwann cells are conducive to nerve repair," say the authors.

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.

Reference: Sakaue, M. and Sieber-Blum, M. (2015). Human epidermal neural crest stem cells as a source of Schwann cells. Development, doi:10.1242/dev.123034

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