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Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine

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Abstract

Traumatic spinal cord injury (SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold (LOCS) and human placenta-derived mesenchymal stem cells (hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment (control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans (CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin (Tuj-1)- and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending (CGRP-positive) sensory fibers and descending (5-HT- and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.

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Acknowledgements

This work was supported by the “Strategic Priority Research Program of the Chinese Academy of Sciences” (XDA01030000), the key Research Program of the Chinese Academy of Sciences (ZDRW-ZS-2016-2), the National Natural Science Foundation of China (81572131, 81571213), the Natural Science Foundation of Jiangsu Province (BL2012004, BK20151210), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the key Research and Development Program of Ministry of Science and Technology (2016YFC1101500).

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Authors and Affiliations

  1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China

    Sufang Han, Zhifeng Xiao, Xing Li, Bin Wang, Bing Chen, Jin Han & Jianwu Dai

  2. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China

    Huan Zhao, Zhixue Qiu, Zhi Li, Xin Mei, Yanzheng Gu, Huilin Yang & Qin Shi

  3. Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China

    Bai Xu & Caixia Fan

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  1. Sufang Han
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  2. Zhifeng Xiao
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  3. Xing Li
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  4. Huan Zhao
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  12. Jin Han
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Correspondence to Qin Shi or Jianwu Dai.

Electronic supplementary material

Figure S1

The morphological and phenotypic profiles of hPMSCs.

Figure S2 Characterization of the LOCS and the surgical procedures for the complete SCI.

Table S1 Assessment of pelvic limb function by Olby score

Movie S1 The movement video of a dog in control group.

Movie S2 The movement video of a dog in LOCS group.

Movie S3 The movement video of a dog in LOCS+hPMSCs group.

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Han, S., Xiao, Z., Li, X. et al. Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine. Sci. China Life Sci. 61, 2–13 (2018). https://doi.org/10.1007/s11427-016-9002-6

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