NU 2023-116

INVENTORS

Nozomu Takata

Nicholas Sather

Samuel Stupp*

SHORT DESCRIPTION

A human organoid model to simulate spinal cord injury in vitro and test potential therapeutics.

BACKGROUND

Injury in organs triggers cellular and molecular rearrangements that induce intrinsic repair and regeneration, but the human central nervous system has a poor capacity for regeneration. For example, following spinal cord injury (SCI), the normal communication to and from the spinal cord can be disrupted, leading to neurodegeneration and irreversible paralysis in humans. Existing experimental in vitro models of human spinal cords are scarce and fail to recapitulate the injury environment and associated glial scars of human patients, hampering research into finding novel SCI therapeutics.

ABSTRACT

Northwestern researchers have developed large human stem cell-derived spinal cord organoids comprising neural cells and glial cells with an undetectable level of immune or vascular cell types. Following mechanical injury, the human spinal cord organoids reveal immediate neuronal death and develop localized glial scar tissue reminiscent to what occurs in human SCI. Additionally, a pre-clinical therapy for SCI (previously investigated in an in vivo mouse model) prevented the glial scar formation and promoted axon regeneration and neurite expansion of the injured organoids. This organoid system is capable of modeling human spinal cord specific responses to SCI and can functions as a scalable platform for testing candidate SCI therapeutics.

APPLICATIONS

• Organoid system for modeling human spinal cord injury in vitro.

• Platform for testing spinal cord injury therapeutics.

• Organoid system for modeling human spinal cord injury in vitro.

• Platform for testing spinal cord injury therapeutics.

ADVANTAGES

• Scalable platform for testing candidate therapeutic molecules

• Capable of recapitulating human-specific responses to spinal cord injury in vitro

• Large size (~3 mm) to enable mechanical injuries for investigating glial scar formation and axon

  regeneration.

IP STATUS

US patent application filed.

Human spinal cord organoids respond to mechanical injury in vitro, forming GFAP+ scar-like tissues next to TUJ-1+ neurons