Tissue Eng Regen Med.  2021 Jun;18(3):467-478. 10.1007/s13770-020-00329-6.

Mesenchymal Stem Cells Derived from Wharton’s Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts

• Choi SJ
• Park SY
• Shin YH
• Heo SH
• Kim KH
• Lee HI
• Kim JK

• KMID: 2516532
• DOI: http://doi.org/10.1007/s13770-020-00329-6

Abstract

BACKGROUND
Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury.
METHODS
The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining.
RESULTS
Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs. WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury.
CONCLUSION
WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

Keyword

Acellular nerve grafts; Schwann cell-like cells; Wharton’s jelly-derived mesenchymal stem cells; Nerve repair