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SCIENCE CHINA Life Sciences, Volume 62, Issue 6: 725-733(2019) https://doi.org/10.1007/s11427-019-9490-8

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

He Shen1,†, Xi Chen3,†, Xing Li2,4,†, Ke Jia3, Zhifeng Xiao2, Jianwu Dai1,2,*
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  • ReceivedJan 12, 2019
  • AcceptedJan 22, 2019
  • PublishedMar 20, 2019

Abstract

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts (aSCGs) as donor constructs for repairing complete spinal cord injury (SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors (brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.


Funded by

grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020100)

the Key Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-2)


Acknowledgment

This work was supported by grants from the National Natural Science Foundation of China (81891002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020100).


Interest statement

The author(s) declare that they have no conflict of interest.


Supplement

SUPPORTING INFORMATION

Figure S1ƒPhoto images of the transection injured spinal cords with or without aSCGs transplantation at 1-, 4- and 12-week post treatment, respectively.

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    A schematic diagram illustrating transplantation of spinal cord tissue grafts from adult rats to a transected SCI model immediately after injury.

  • Figure 2

    GFP labelled the spinal cord segments of the adult donors. Representative immunofluorescence images of double staining with GFP and (A) MAP2, (B) ALDH1L1, (C) S100A4, (D) NG2, (E) APC, (F) MBP, and (G) RECA in the aSCGs, respectively. The insets of GFP/ALDH1L1 and GFP/APC: lower magnification images.

  • Figure 3

    The survival of the transplanted aSCGs. Immunofluorescence images of the injured host spinal cord and transplanting aSCGs with or without addition of growth factors. GFP (green) represents the cells in donor segments, GFAP (red) represents the astrocytes in both donor and host tissues at 1, 4 and 12 weeks after surgery, respectively.

  • Figure 4

    Immunofluorescence images of the lesion area in the control, T and T+G groups at 1, 4 and 12 weeks after transplantation, respectively. Tuj-1 (red) indicates the neurons at the lesion sites. Scale bar, 100 µm.

  • Figure 5

    Surviving cell types in the engrafted aSCGs in the T+G group. Representative immunofluorescence images of double staining with MAP2/GFP, ALDH1L1/GFP, S100A4/GFP, NG2/GFP, APC/GFP, MBP/GFP, and RECA/GFP in the aSCGs at 1-, 4-, and 12-week post-treatment, respectively. Scale bar, 100 µm.

  • Figure 6

    Transplantation of the aSCGs enhanced electrophysiological recovery and locomotor function improvement. A, MEP (motor evoked potential) recording of rats in SCI, T and T+G groups at x post-surgery, respectively. (B) Latent periods and (C) amplitude of MEP results of different groups. Values are mean±SD. *, P<0.05; **, P<0.01. D, Locomotor function test curves in BBB scoring system of normal, SCI, T and T+G groups from surgery to 12 weeks postinjury. Values are mean±SD. **, P<0.01 comparing T+G group with SCI (control) group.

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