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Injury and Treatment of a Human Spinal Cord Organoid II [scRNA-seq]

ABSTRACT: Damage of the spinal cord, which can lead to irreversible paralysis and loss of sensory function, is among the most devastating injuries suffered by humans. A significant effort has been made over the past few decades to find potential therapies to treat spinal cord injury (SCI), an objective that faces the challenge of central nervous system regeneration. Experimental access to human spinal cord tissue is therefore a critical need for discovery of SCI therapies and thus availability of the organ mimics known as organoids offers great potential. Research on spinal cord organoids has been sparse and only very recently enabled by the discovery of the necessary human progenitor cells derived from pluripotent stem cells. We report here on a human organoid model to simulate SCI in vitro and test the potential of novel therapies. We found that the model, involving injury of the organoid with a sharp scalpel, reveals immediate neuronal death and subsequently generates the characteristic glial scar observed after injury with its biological markers. Exposure of the injured organoid to a recently discovered pre-clinical therapy for SCI avoids formation of the scar and promotes axon regeneration in the area of the lesion. Furthermore, in the absence of injury we directly observed the activation of the developmental program to extend axons by the tested therapy, which contains bioactive nanofibers with intense supramolecular motion. The model developed here could accelerate discovery of therapeutic strategies to treat the broad spectrum of spinal cord injuries.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267067 | GEO | 2025/10/03

REPOSITORIES: GEO

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Injury and Treatment of a Human Spinal Cord Organoid [scRNA-seq]

Project description:Damage of the spinal cord, which can lead to irreversible paralysis and loss of sensory function, is among the most devastating injuries suffered by humans. A significant effort has been made over the past few decades to find potential therapies to treat spinal cord injury (SCI), an objective that faces the challenge of central nervous system regeneration. Experimental access to human spinal cord tissue is therefore a critical need for discovery of SCI therapies and thus availability of the organ mimics known as organoids offers great potential. Research on spinal cord organoids has been sparse and only very recently enabled by the discovery of the necessary human progenitor cells derived from pluripotent stem cells. We report here on a human organoid model to simulate SCI in vitro and test the potential of novel therapies. We found that the model, involving injury of the organoid with a sharp scalpel, reveals immediate neuronal death and subsequently generates the characteristic glial scar observed after injury with its biological markers. Exposure of the injured organoid to a recently discovered pre-clinical therapy for SCI avoids formation of the scar and promotes axon regeneration in the area of the lesion. Furthermore, in the absence of injury we directly observed the activation of the developmental program to extend axons by the tested therapy, which contains bioactive nanofibers with intense supramolecular motion. The model developed here could accelerate discovery of therapeutic strategies to treat the broad spectrum of spinal cord injuries.

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Injury and Therapy in a Human Spinal Cord Organoid

Project description:Damage to the spinal cord, which can lead to irreversible paralysis and loss of sensory function, is among the most devastating injuries suffered by humans. A significant effort has been made over the past few decades to find therapies to treat spinal cord injury (SCI) but translation of pre-clinical work remains elusive. Experimental access to human spinal cord tissue is therefore critical to accelerate discovery of effective SCI therapies. Thus, availability of the organ mimics known as organoids offers great potential for this important objective. We report here on the development of two human organoid injury models to simulate SCI in vitro, using as a therapy bioactive supramolecular assemblies of peptide amphiphiles. The system tested here has been recently shown to be highly effective at reversing paralysis in an acute murine model following severe SCI. The models use either a laceration of the organoid with a scalpel or a compressive contusion commonly used in preclinical models. We found that both injuries result in immediate neuronal death and interestingly generate glial scar-like tissue. Exposure of the injured organoids to the pre-clinical therapy validated in vivo avoided formation of the scar-like tissue and promoted significant axonal regeneration. Furthermore, in the absence of injury, we directly observed the activation of the developmental program that extends neurites as a result of the therapy. Our observations indicate that injury models on human organoids could accelerate the discovery of therapies to treat spinal cord injury and possibly damage of other central nervous system tissues due to trauma or disease.

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