An injectable decellularized extracellular matrix hydrogel with cortical neuron-derived exosomes enhances tissue repair following traumatic spinal cord injury

Materials Today Bio, 2024 · DOI: https://doi.org/10.1016/j.mtbio.2024.101250 · Published: September 14, 2024

Regenerative Medicine Neurology Biomedical

Simple Explanation

Traumatic spinal cord injury (SCI) often results in considerable neurological impairment because of its limited regeneration capacity. Exosomes show promise for SCI treatment by promoting tissue regeneration. Combining exosome therapy with biomaterials may improve SCI treatment effectiveness. This study developed an adhesive hydrogel using exosomes secreted by cortical neurons derived from human induced pluripotent stem cells (iPSCs) and decellularized extracellular matrix (dECM) from human umbilical cord mesenchymal stem cells (hUCMSCs). The Exo-dECM hydrogel was created to enhance motor function recovery post-SCI. The Exo-dECM hydrogel facilitated the polarization of early M2 macrophages, reduced neuronal apoptosis, and established a pro-regenerative microenvironment in a rodent SCI model. The Exo-dECM hydrogel also promoted the functional recovery and preservation of urinary tissue in SCI-afflicted rats.

Study Duration

8 Weeks

Participants

Healthy adult female Sprague‒Dawley rats (200–220 g)

Evidence Level

Not specified

Key Findings

1
The Exo-dECM hydrogel exhibited robust mechanical stability and excellent cytocompatibility, allowing effective injection into the injury site to fill the lesion cavity.
2
Following implantation of the Exo-dECM hydrogel, significant polarization of M2 macrophages and activation of endogenous neural stem cells were observed.
3
Axon regeneration and remyelination were facilitated at eight weeks post-implantation. Additionally, improvements in functional recovery were observed in a rat SCI model.

Research Summary

This study developed an injectable adhesive Exo-dECM hydrogel comprising a decellularized extracellular matrix and exosomes derived from cortical neurons as a potential therapeutic intervention for SCI. The Exo-dECM hydrogel was found to enhance the local microenvironment, mitigate neuronal apoptosis in the early stages, and promote functional recovery by activating endogenous neural stem cells, facilitating axon regeneration, and supporting remyelination in rats with SCI. This novel approach of combining cortical neuron-derived exosomes with decellularized extracellular matrix-based hydrogels represents a promising strategy for treating traumatic SCI.

Practical Implications

Therapeutic Strategy

The Exo-dECM hydrogel shows potential as a therapeutic approach for SCI treatment by enhancing the microenvironment and promoting tissue repair.

Delivery System

The dECM hydrogel serves as an effective delivery system for cortical neuron-derived exosomes, ensuring sustained release and localized action at the injury site.

Clinical Translation

Further research and development of Exo-dECM hydrogels could lead to innovative clinical applications for SCI patients, improving functional outcomes and quality of life.

Study Limitations

1
The study exclusively used female rats, which may introduce gender-specific effects due to hormone fluctuations.
2
Current dECM hydrogels lack structural organization, and the injectable delivery system used here was designed for single-treatment applications.
3
The molecular mechanisms underlying the therapeutic effects of Exo-dECM hydrogels in improving the microenvironment and promoting tissue repair are only partially understood.

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