Injury and therapy in a human spinal cord organoid

Area of Science:

• Neuroscience
• Regenerative Medicine
• Biomaterials Science

Background:

• Spinal cord injury (SCI) causes irreversible paralysis, with limited success in translating preclinical therapies.
• Previous work demonstrated peptide amphiphile nanomaterials can reverse paralysis in mouse models of acute SCI.

Purpose of the Study:

• To develop human spinal cord organoid models simulating SCI for in vitro testing.
• To evaluate the efficacy of a preclinical peptide amphiphile therapy in these novel organoid models.

Main Methods:

• Development of two human spinal cord organoid injury models: laceration and contusion.
• Treatment of injured organoids with bioactive supramolecular assemblies of peptide amphiphiles.
• Assessment of glial scar formation, axonal regeneration, and inflammatory factors (with microglia inclusion).

Main Results:

• Both injury models induced neuronal death and glial scar-like tissue formation.
• Therapy suppressed scar-like tissue and significantly promoted axonal regeneration in vitro.
• The nanomaterial reduced pro-inflammatory factors in organoids containing microglia.

Conclusions:

• Human spinal cord organoid models provide a viable platform for simulating SCI in vitro.
• The tested peptide amphiphile therapy shows promise for promoting regeneration and reducing inflammation after SCI.
• These organoid models can accelerate the discovery of treatments for SCI and other central nervous system injuries.