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The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats

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Abstract

Inflammatory response following spinal cord injury (SCI) is important in regulation of the repair process. Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are important donor cells for repairing SCI in different animal models. However, synergistic or complementary effects of co-transplantation of both cells for this purpose have not been extensively investigated. In the present study, we investigated the effects of co-transplantation of OECs and SCs on expression of pro- or anti-inflammatory factor and polarization of macrophages in the injured spinal cord of rats. Mixed cell suspensions containing OECs and SCs were transplanted into the injured site at 7 days after contusion at the vertebral T10 level. Compared with the DMEM, SC, or OEC group, the co-transplantation group had a more extensive distribution of the grafted cells and significantly reduced number of astrocytes, microglia/macrophage infiltration, and expression of chemokines (CCL2 and CCL3) at the injured site. The co-transplantation group also significantly increased arginase+/CD206+ macrophages (IL-4) and decreased iNOS+/CD16/32+ macrophages (IFN-γ), which was followed by higher IL-10 and IL-13 and lower IL-6 and TNF-α in their expression levels, a smaller cystic cavity area, and improved motor functions. These results indicate that OEC and SC co-transplantation could promote the shift of the macrophage phenotype from M(IFN-γ) to M(IL-4), reduce inflammatory cell infiltration in the injured site, and regulate inflammatory factors and chemokine expression, which provide a better immune environment for SCI repair.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81371341); Funds of the State Key Laboratory of Trauma, Burn and Combined Injury (SKLZZ201003); Special Funds for Major State Basic Research Project, China (2012CB518106); and Youth Innovation Funds of Research Institute of Surgery, Third Military Medical University (2014YQN07).

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Authors and Affiliations

  1. State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing, 400042, China

    Jieyuan Zhang, Huijun Chen, Zhaoxia Duan, Kuijun Chen, Zeng Liu, Lu Zhang, Dongdong Yao & Bingcang Li

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  1. Jieyuan Zhang
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Correspondence to Bingcang Li.

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All the animals were housed according to the Third Military Medical University (TMMU) guidelines, and surgical procedures and post-operative care were conducted in accordance with protocols approved by the TMMU Institutional Animal Care and Use Committee.

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Zhang, J., Chen, H., Duan, Z. et al. The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats. Mol Neurobiol 54, 943–953 (2017). https://doi.org/10.1007/s12035-016-9709-5

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  • DOI: https://doi.org/10.1007/s12035-016-9709-5

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