Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (10): 1903-1911.doi: 10.4103/1673-5374.280330

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Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration

Yang Zhang1, Wen-Tao Wang2, Chun-Rong Gong3, Chao Li4, Mei Shi1   

  1. 1 Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China
    2 Department of Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, China
    3 Rehabilitation Center, North District Hospital of the People’s Hospital of Lin Yi City, Linyi, Shandong Province, China
    4 Department of Orthopedics, The Eighth Medical Center of Chinese PLA general Hospital, Beijing, China
  • Online:2020-10-15 Published:2020-08-19
  • Contact: Mei Shi, PhD, mshi82@hotmail.com; Chao Li, PhD, Chnmedli@126.com.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, No. 81872699 (to MS), Key project of Shaanxi Province, China, No. 2017ZDXM-SF-043 (to MS), and the Military Medical Science and Technology Youth Development Program, China, No. 19QNP061 (to CL).

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Abstract: Olfactory ensheathing cells (OECs) are promising seed cells for nerve regeneration. However, their application is limited by the hypoxic environment usually present at the site of injury. Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia. The ability of OECs to migrate is unknown, especially in hypoxic conditions, and the effect of OECs combined with exosomes on peripheral nerve repair is not clear. Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed. In this study, OECs were acquired from the olfactory bulb of Sprague Dawley rats. Human umbilical cord mesenchymal stem cell-derived exosomes (0–400 μg/mL) were cultured with OECs for 12–48 hours. After culture with 400 μg/mL exosomes for 24 hours, the viability and proliferation of OECs were significantly increased. We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes. Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions, and effectively increased brain-derived neurotrophic factor gene expression, protein levels and secretion. Finally, using a 12 mm left sciatic nerve defect rat model, we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve. These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery. This study was approved by the Institutional Ethical Committee of the Air Force Medical University, China (approval No. IACUC-20181004) on October 7, 2018; and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital, China (approval No. 30054) on May 20, 2019.

Key words: brain-derived neurotrophic factor, cell migration, cell viability, functional recovery, hypoxia, nerve regeneration, sciatic functional index, sciatic nerve injury