Open Access

Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury

  • Authors:
    • Tingting Li
    • Xiaoyang Zhao
    • Jing Duan
    • Shangbin Cui
    • Kai Zhu
    • Yong Wan
    • Shaoyu Liu
    • Zhiming Peng
    • Le Wang
  • View Affiliations

  • Published online on: May 3, 2021     https://doi.org/10.3892/etm.2021.10143
  • Article Number: 711
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

STAT3 is expressed in neural stem cells (NSCs), where a number of studies have previously shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and role of STAT3 in spinal cord injury (SCI) remain unclear. In the present study, the potential effect of STAT3 in NSCs was first investigated by using short hairpin RNA (shRNA)‑mediated STAT3 knockdown in rat NSCs in vitro. Immunofluorescence of β3‑tubulin and glial fibrillary acidic protein staining and western blotting showed that knocking down STAT3 expression promoted NSC neuronal differentiation, where the activity of mTOR was upregulated. Subsequently, rats underwent laminectomy and complete spinal cord transection followed by transplantation of NSCs transfected with control‑shRNA or STAT3‑shRNA at the injured site in vivo. Spinal cord‑evoked potentials and the Basso‑Beattie‑Bresnahan scores were used to examine functional recovery. In addition, axonal regeneration and tissue repair were assessed using retrograde tracing with FluoroGold, hematoxylin and eosin, Nissl and immunofluorescence staining of β3‑tubulin, glial fibrillary acidic protein and microtubule‑associated protein 2 following SCI. The results showed that transplantation with NSCs transfected with STAT3‑RNA enhanced functional recovery following SCI and promoted tissue repair in rats, in addition to improving neuronal differentiation of the transplanted NSCs in the injury site. Taken together, in vitro and in vivo evidence that inhibiting STAT3 could promote NSC neuronal differentiation was demonstrated in the present study. Therefore, transplantation with NSCs with STAT3 expression knocked down appears to hold promising potential for enhancing the benefit of NSC‑mediated regenerative cell therapy for SCI.

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July-2021
Volume 22 Issue 1

Print ISSN: 1792-0981
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Spandidos Publications style
Li T, Zhao X, Duan J, Cui S, Zhu K, Wan Y, Liu S, Peng Z and Wang L: Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury. Exp Ther Med 22: 711, 2021
APA
Li, T., Zhao, X., Duan, J., Cui, S., Zhu, K., Wan, Y. ... Wang, L. (2021). Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury. Experimental and Therapeutic Medicine, 22, 711. https://doi.org/10.3892/etm.2021.10143
MLA
Li, T., Zhao, X., Duan, J., Cui, S., Zhu, K., Wan, Y., Liu, S., Peng, Z., Wang, L."Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury". Experimental and Therapeutic Medicine 22.1 (2021): 711.
Chicago
Li, T., Zhao, X., Duan, J., Cui, S., Zhu, K., Wan, Y., Liu, S., Peng, Z., Wang, L."Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury". Experimental and Therapeutic Medicine 22, no. 1 (2021): 711. https://doi.org/10.3892/etm.2021.10143