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Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury
Author(s) -
Li Xiang,
Peng Zhiming,
Long Lingli,
Tuo Ying,
Wang Liqin,
Zhao Xiaoyang,
Le Wang,
Wan Yong
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901478rr
Subject(s) - transplantation , spinal cord injury , spinal cord , notch signaling pathway , neural stem cell , neuroscience , astrocyte , medicine , stem cell , biology , central nervous system , microbiology and biotechnology , signal transduction
Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, yet there are no effective therapies currently due to the failure of reconstructing the interruption of the neuroanatomical circuit. While neural stem cell (NSC) transplantation has been considered a potential strategy to repair the neural circuit after SCI, the efficacy of this strategy remains unproven. The main reason is that most of the transplanted NSC differentiates into astrocyte rather than neuron in the microenvironment of SCI. Our results demonstrated that Wnt4 significantly promotes the differentiation of NSC into neuron by activating both β‐catenin and MAPK/JNK pathways and suppressing the activation of Notch signaling, which is acknowledged as prevention of NSC differentiation into neuron, through downregulating NICD expression, translocating and preventing the combination of NICD and RbpJ in nucleus. In addition, Wnt4 rescues the negative effect of Jagged, the ligand of Notch signaling, to promote neuronal differentiation. Moreover, in vivo study, transplantation of Wnt4‐modified NSC efficaciously repairs the injured spinal cord and recovers the motor function of hind limbs after SCI. This study sheds new light into mechanisms that Wnt4‐modified NSC transplantation is sufficient to repair the injured spinal cord and recover the motor dysfunction after SCI.