LPC18:0 Secreted by Exogenous Neural Stem Cells Potentiates Neurogenesis and Functional Recovery via GPR55-Mediated...

Area of Science:

• Neuroscience
• Regenerative Medicine
• Metabolomics

Background:

• Spinal cord injury (SCI) presents significant therapeutic challenges due to the inhibitory post-injury microenvironment.
• Neural stem cell (NSC) transplantation offers regenerative potential but is limited by these environmental factors.

Purpose of the Study:

• To investigate metabolic reprogramming following NSC transplantation in a rat SCI model.
• To identify key metabolites mediating NSC therapeutic effects and elucidate their mechanisms.

Main Methods:

• Untargeted metabolomics was employed to analyze metabolic changes in a rat SCI model with NSC-loaded scaffolds.
• Functional recovery, structural remodeling, neurogenesis, and gliosis were assessed.
• The role of identified metabolites and signaling pathways (GPR55/AKT/GSK3β) was investigated using receptor-specific inhibition and in vivo administration.

Main Results:

• NSC transplantation improved functional recovery, enhanced neurogenesis, reduced gliosis, and promoted structural remodeling.
• Lysophosphatidylcholine 18:0 (LPC18:0) was identified as a crucial NSC-derived metabolite.
• LPC18:0 promoted endogenous NSC differentiation into neurons via the GPR55/AKT/GSK3β pathway, improving motor function and axonal regeneration in vivo.

Conclusions:

• This study reveals a novel metabolic mechanism for NSC-based spinal cord injury therapy.
• Lysophosphatidylcholine 18:0 (LPC18:0) acts as a key mediator of NSC therapeutic effects.
• The LPC18:0/GPR55/AKT/GSK3β signaling axis represents a promising therapeutic target for enhancing spinal cord injury recovery.