Bone marrow mesenchymal stem cells modified with the neurotrophic factor-3 gene combined with hydrogels for the treatment of spinal cord injury in rats
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Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100021, China

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    Abstract:

    Objective To investigate the therapeutic effects of the combination of bone marrow mesenchymal stem cells ( BMSCs), neurotrophic factor 3 ( NT-3), and hydrogels on spinal cord injury. Methods Rat BMSCs were genetically modified to overexpress NT-3, and hydrogels were prepared and loaded with the modified cells. Then, a model of acute incomplete spinal cord injury in rats was established and treated. The combined therapeutic effect on spinal cord injury was assessed by postoperative motor behavior (Basso Beatlie Bresnahan (BBB) score) and spinal cord pathology. Results The motor behavioral BBB scores of rats in the combination therapy group were increased by various degrees, and the therapeutic effect of the BMSC+NT-3+hydrogel group was the most obvious. Immunohistochemistry showed that the degree of nerve recovery in the combined treatment group was higher than that in the spinal cord injury model group. The numbers of neurons and nerve fibers were increased in all combined treatment groups, while the number of astrocytes was decreased. In the treatment groups, the BMSC+NT-3+hydrogel group had the highest number of neurons and nerve fibers and the lowest number of astrocytes. The difference between all groups was statistically significant ( P < 0. 05 ). Conclusions BMSCs, NT-3, and a hydrogel scaffold promoted each other and can be combined to better treat spinal cord injury. By transplanting into rats with acute incomplete spinal cord injury, they promoted post-injury neuronal and nerve fiber repair and inhibited the formation of glial scars. The preparation of more effective and injectable composites may provide a new concept for nerve repair and regeneration in spinal cord injury.

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History
  • Received:April 28,2020
  • Revised:
  • Adopted:
  • Online: August 25,2020
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