Abstract
Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.
Highlights
In contrast to the poor regenerative capacity of the central nervous system (CNS), the peripheral nervous system can regenerate after injury
The current study demonstrates that, unlike CNS, developing Schwann cells (SCs) have no capacity to support the regeneration of adult axons after peripheral nerve injury (PNI), that developing SCs are distinctly different from repair SCs (RSCs) in molecular and functional aspects, and that RSC is a potent candidate as a graft cell type for axon regeneration therapy after PNI
SCs develop from neural crest cells, differentiate to SC precursors (SCPs) around E14 (Fig. 1a) and to immature SCs (ISCs) around E18 (Fig. 1b)[34,35]
Summary
In contrast to the poor regenerative capacity of the central nervous system (CNS), the peripheral nervous system can regenerate after injury. Due to the recent advancement of biomaterials, new treatment options such as a synthetic scaffold or decellularized allograft became clinically available to overcome the issues derived from ANG6,7. Their axon-promoting effects are still not comparable to ANG. With the rapid growth of stem cell research, novel SC-like cells have been developed as a new graft material. They have differentiated from various kinds of stem cells[22,23,24,25,26] or fibroblasts with direct reprogramming technique[27]
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