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

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Tissue Engineering and Regenerative Medicine Aims and scope

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-SCLCs-laden 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 S100β, 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.

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Acknowledgements

We thank the Stem Cell Institute at Asan Medical Center for providing the WJ-MSCs and the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT) for support and instrumentation. This study was supported by a grant from Asan Institute for Life Sciences, Asan Medical Center, Republic of Korea (#2019IP0766-1, 2020IP0079-1) and by the National Research Foundation of Korea (NRF-2017R1A2B4003692, 2020R1A2C1006656), funded by the Ministry of Science, ICT, and Future Planning.

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Authors and Affiliations

  1. Asan Peripheral Nerve Regeneration Lab Institute for Life Sciences, Seoul, South Korea

    Soon Jin Choi, Suk Young Park & Jae Kwang Kim

  2. Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic Road 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Young Ho Shin & Jae Kwang Kim

  3. Convergence Medicine Research Center, Asan Medical Center, Seoul, South Korea

    Seung-Ho Heo, Kang-Hyun Kim & Hyo In Lee

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  1. Soon Jin Choi
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Correspondence to Jae Kwang Kim.

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The study protocol was approved by the Asan Medical Center Institutional Review Board (#2015-0303), which waived the need for informed consent. All animal studies were performed after receiving approval from the Institutional Animal Care and Use Committee at Asan Medical Center (#2017-12-127).

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Choi, S.J., Park, S.Y., Shin, Y.H. et al. Mesenchymal Stem Cells Derived from Wharton’s Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts. Tissue Eng Regen Med 18, 467–478 (2021). https://doi.org/10.1007/s13770-020-00329-6

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