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Curcumin-Primed Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles Improve Motor Functional Recovery of Mice with Complete Spinal Cord Injury by Reducing Inflammation and Enhancing Axonal Regeneration

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Abstract

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo. Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.

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Funding

This work was supported by the Natural Science Foundation of China (Project No. 81871781) and the Key Project of Natural Science Foundation of Heilongjiang Province of China (Project No. ZD2021H003).

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Authors and Affiliations

  1. Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Wei Xiong, Zhibin Peng & Yansong Wang

  2. Department of Spinal Surgery, Yantaishan Hospital, Yantai, China

    Haiqing Tian

  3. The Fifth Department of Orthopedics, Affiliated Hospital of Chifeng University, Chifeng, China

    Zhigang Li

  4. NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin, China

    Yansong Wang

  5. Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, Harbin Medical University, Harbin, China

    Yansong Wang

  6. No.2075, Qunli Seventh Avenue, Daoli District, Harbin, China

    Yansong Wang

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  1. Wei Xiong
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Haiqing Tian, Zhigang Li and Zhibin Peng. The first draft of the manuscript was written by Wei Xiong. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yansong Wang.

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This study was performed in line with the principles of the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, eighth edition, 2011). Approval was granted by the First Affiliated Hospital of Harbin Medical University (Approval No. 202103028-018).

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Xiong, W., Tian, H., Li, Z. et al. Curcumin-Primed Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles Improve Motor Functional Recovery of Mice with Complete Spinal Cord Injury by Reducing Inflammation and Enhancing Axonal Regeneration. Neurochem Res 48, 1334–1346 (2023). https://doi.org/10.1007/s11064-022-03832-5

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