The Success and Failure of the Schwann Cell Response to Nerve Injury

Abstract

The remarkable plasticity of Schwann cells allows them to adopt the Remak (non-myelin) and myelin phenotypes, which are specialized to meet the needs of small and large diameter axons, and differ markedly from each other. It also enables Schwann cells initially to mount a strikingly adaptive response to nerve injury and to promote regeneration by converting to a repair-promoting phenotype. These repair cells activate a sequence of supportive functions that engineer myelin clearance, prevent neuronal death, and help axon growth and guidance. Eventually, this response runs out of steam, however, because in the long run the phenotype of repair cells is unstable and their survival is compromised. The re-programming of Remak and myelin cells to repair cells, together with the injury-induced switch of peripheral neurons to a growth mode, gives peripheral nerves their strong regenerative potential. But it remains a challenge to harness this potential and devise effective treatments that maintain the initial repair capacity of peripheral nerves for the extended periods typically required for nerve repair in humans.

Advances in the repair of segmental nerve injuries and trends in reconstruction

“…Distal to the injury site, the process of Wallerian degeneration is initiated, which involves the fragmentation of axons disconnected from the neuron, and nonneuronal cell activation that primes the distal nerve environment for new axon outgrowth. Schwann cells (SCs) sensing the axon damage dedifferentiate and adopt a unique “repair” phenotype . SC signaling involved in this dedifferentiation relies on Notch signaling and extracellular signal‐regulated kinase‐mediated signaling pathways, and is orchestrated by the phosphorylation of c‐Jun .…”

Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration

“…Bucan et al showed rat ADSC-exosomes to contain a range of neurotrophic factors, such as glial-cell derived neurotrophic factor, FGF-1, BDNF, ILGF-1, as well as nerve growth factor (NGF) (Bucan et al, 2019). Schwann cells are also simulated by neurotrophic factors NGF and BDNF and elicited pro-regenerative effects in nerve regeneration after nerve damage (Jessen and Mirsky, 2019). Chen et al also demonstrated that exosomes derived from human ADSCs enhanced secretion of BDNF and NGF by Schwann cells, which led to increased proliferation, myelination, migration of cells in a dose-dependent manner in vitro .…”

Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8

“…On the other hand, understanding how tumor cells induce and maintain a repair SC state in benignly behaving GNB/GN could enable a therapeutic induction of SC stroma in aggressive NBs. Furthermore, identifying how the repair SC state can be sustained is also of high value for the field of regenerative medicine, since one of the main reasons for axonal regeneration failure after injury is the deterioration of repair SCs over time Page 34 of 48 (Jessen & Mirsky, 2019). Thus, the more detailed knowledge about the molecular processes involved in GNB/GN development and nerve regeneration is promising to enrich treatment approaches for both nerve repair and aggressive NBs.…”