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A Direct Solution to a Schwann cell Problem?

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Review of “Direct Conversion of Human Fibroblasts into Schwann Cells That Facilitate Regeneration of Injured Peripheral Nerve In Vivo” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Schwann cells (SCs) play important roles in the maintenance and regulation of the peripheral nerve system (PNS) and for these reasons, many hope to employ SCs to regenerate damaged nerves. However, the collection of sufficient numbers of human primary (p)SCs for transplantation purposes remains a substantial problem.

Now, a new STEM CELLS Translational Medicine study from the laboratory of Osam Mazda (Kyoto Prefectural University of Medicine, Japan) may have the answer to the Schwan cell problem: the direct conversion of human fibroblasts into dSCs via the forced expression of SC-specific transcription factors [1].

To induce reprogramming of human fibroblasts to an SC fate, the authors overexpressed two transcription factors (Sex10 and Krox20) linked to the SC fate in the presence of SC differentiation medium [2, 3]. Transient expression of these two factors induced the expression of SC markers (p75NTR, GFAP, and NG2) and forced the reprogrammed cells to take on the typical spindle-shaped SC morphology, altogether suggesting an equivalence of dSCs with the difficult to isolate pSCs. 

dSCs and pSCs also displayed similarities at the functional level; dSCs secreted important neurotrophic factors (e.g. BDNF, NGF, and GDNF) and promoted neurite outgrowth during co-culture of neuronal cells. Furthermore, dSCs also displayed myelin-forming activity when in proximity to neural cells during in vitro co-culture experiments and in vivo following transplantation into a segmental defect in the sciatic nerve of nude mice (See Figure). Encouragingly, in vivo studies also indicated that dSC transplants accelerated peripheral nerve regeneration and improved motor function in a similar manner to transplanted pSCs, indicating their potent glial function.

Overall, we may have a direct solution to a Schwann cell problem, as these data suggest that dSC transplantation provides similar benefits to the transplantation of primary SCs which are more difficult to collect in sufficient numbers. The authors note that while this represents an exciting opportunity for the treatment of peripheral nerve injury in a patient-specific and safe manner, dSCs may also find use in the treatment of central nervous system damage and for neurodegenerative disorders related to SC dysfunction. 

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References

  1. Sowa Y, Kishida T, Tomita K, et al. Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo. STEM CELLS Translational Medicine 2017;6:1207-1216.
  2. Stolt CC and Wegner M. Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination. Brain Res 2016;1641:101-110.
  3. Monk KR, Feltri ML, and Taveggia C. New insights on Schwann cell development. Glia 2015;63:1376-1393.