Neural Regeneration Research ›› 2018, Vol. 13 ›› Issue (1): 145-153.doi: 10.4103/1673-5374.224383

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Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve

NaRi Seo1, 3, Sung-Ho Lee2, 3, Kyung Won Ju2, 3, JaeMan Woo2, BongJu Kim4, SoungMin Kim1, 2, Jeong Won Jahng3, Jong-Ho Lee1, 2, 3, 4   

  1. 1 Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Seoul National University, Seoul, South Korea
    2 Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, South Korea
    3 Dental Research Institute, Seoul National University, Seoul, South Korea
    4 Clinical Translational Research Center for Dental Science (CTRC), Seoul National University Dental Hospital, Seoul, South Korea
  • Received:2017-12-02 Online:2018-01-15 Published:2018-01-15
  • Contact: Jong-Ho Lee, D.D.S., M.S.D.,Ph.D., leejongh@snu.ac.kr.
  • Supported by:

    This study was supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1535).

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Abstract:

Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments.In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 106 cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and more DiI-labeled neurons in the trigeminal ganglia, contributing to rapider functional recovery of injured mental nerve. These findings suggest that low-frequency PEMF pretreatment is a promising approach to enhance the efficacy of cell therapy for peripheral nerve injury repair.

Key words: nerve regeneration, mesenchymal stem cells, low-frequency pulsed electromagnetic field, peripheral nerve injury, crush-injured mental nerve