Nerve Guidance Conduit - Cellular Therapies - Stem Cells - Ectomesenchymal Stem Cells (EMSCs)

Ectomesenchymal Stem Cells (EMSCs)

The difficulty of isolating Schwann cells and subsequently inducing proliferation is a large obstacle. A solution is to selectively induce cells such as ectomesenchymal stem cells (EMSCs) into Schwann cell-like phenotypes. EMSCs are neural crest cells that migrate from the cranical neural crest into the first branchial arch during early development of the peripheral nervous system. EMSCs are multipotent and possess a self-renewing capacity. They can be thought of as Schwann progenitor cells because they are associated with dorsal root ganglion and motor nerve development. EMSC differentiation appears to be regulated by intrinsic genetic programs and extracellular signals in the surrounding environment. Schwann cells are the source for both neurotropic and neurotrophic factors essential for regenerating nerves and a scaffold for guiding growth. Nie, Zhang et al. conducted a study investigating the benefits of culturing EMSCs within PLGA conduits. Adding foskolin and BPE to an EMSC culture caused the formation of elongated cell processes, which is common to Schwann cells in vitro. Thus, foskolin and BPF may induce differentiation into Schwann cell-like phenotypes. BPE contains the cytokines GDNF, basic fibroblast growth factor and platelet-derived growth factor, which cause differentiation and proliferation of glial and Schwann cells by activating MAP kinases. When implanted into the PLGA conduits, the EMSCs maintained long-term survival and promoted peripheral nerve regeneration across a 10 mm gap, which usually demonstrates little to no regeneration. Myelinated axons were present within the grafts and basal laminae were formed within the myelin. These observations suggest that EMSCs may promote myelination of regenerated nerve fibers within the conduit.