Transplantation of Wnt4-modified neural stem cells mediate M2 polarization to improve inflammatory micro-environment of spinal cord injury

Neural stem cell (NSC) transplantation is a potential strategy for spinal cord injury (SCI) repair, but its effectiveness is limited by the inflammatory environment. Wnt4, known for its neuroprotective and anti-inflammatory properties, could enhance NSC transplantation. This study investigates how Wnt4-modified NSCs interact with macrophages, key contributors to inflammation after SCI. The study reveals that Wnt4-modified NSCs promote M2 polarization (an anti-inflammatory type) and suppress M1 polarization (a pro-inflammatory type) of macrophages by inhibiting the TLR4/NF-κB signaling pathway. In turn, M2 macrophages stimulate neuronal differentiation of NSCs through the MAPK/JNK pathway, creating a positive feedback loop for tissue repair. In animal models, transplantation of Wnt4-modified NSCs improved the inflammatory environment by promoting M2 polarization, leading to enhanced axonal regeneration and tissue repair. These findings suggest that Wnt4-modified NSCs could be a promising therapeutic approach for SCI by modulating the inflammatory response and promoting a regenerative microenvironment.

• 1
  Wnt4-modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages by suppressing the TLR4/NF-κB signaling pathway in a co-culture system.
• 2
  M2 macrophages promote neuronal differentiation of NSCs through the MAPK/JNK signaling pathway, suggesting a reciprocal beneficial interaction.
• 3
  In vivo transplantation of Wnt4-modified NSCs in rats with SCI resulted in increased M2 polarization, reduced M1 polarization, enhanced axonal regeneration, and improved locomotor function.