Effect of Hyaluronic Acid Hydrogels Containing Astrocyte-Derived Extracellular Matrix and/or V2a Interneurons on Histologic Outcomes following Spinal Cord Injury

Biomaterials, 2018 · DOI: 10.1016/j.biomaterials.2018.02.013 · Published: April 1, 2018

Simple Explanation

One of the main reasons for poor recovery after spinal cord injury is the formation of a glial scar, which prevents new axon growth. Astrocytes, which form this scar, can be both helpful and harmful for recovery. This study investigates whether hyaluronic acid (HA) hydrogels containing extracellular matrix (ECM) from astrocytes can improve outcomes after spinal cord injury in rats. The researchers also tested if these hydrogels, with or without ECM, could support the transplantation of V2a interneurons, which are important for spinal cord function. They found that ECM from protoplasmic astrocytes (found in grey matter) reduced the size of the glial scar and increased axon penetration, while also reducing inflammation. HA hydrogels were also able to support the transplantation of V2a interneurons, leading to an increase in neuronal processes in and around the injured area. Overall, the ECM from protoplasmic astrocytes shows promise for treating central nervous system injuries, and ECM:HA hydrogels are a novel scaffold with beneficial effects after spinal cord injury, both with and without cells.

Study Duration

Not specified

Participants

Female Long-Evans rats, 225–275 g

Evidence Level

Not specified

Key Findings

1
ECM harvested from protoplasmic astrocytes, but not fibrous astrocytes, reduced glial scar size, increased axon penetration, and reduced macrophage/microglia staining.
2
HA hydrogels supported V2a interneuron transplantation, increasing neuronal processes within and around the lesion.
3
Protoplasmic mESC-derived astrocyte ECM demonstrates potential for CNS injury treatment and ECM:HA hydrogels represent a novel scaffold with beneficial effects on histologic outcomes after SCI both with and without cells.

Research Summary

This work examines the effect of HA hydrogels containing ECM derived from different mESC-derived astrocyte populations on motoneuron growth in vitro and the effects of these astrocyte ECMs on histologic outcomes in rats following a thoracic dorsal hemisection SCI. The ability of HA hydrogels with and without ECM to support transplantation of mESC-derived V2a interneurons into a SCI lesion is also explored. This work represents the first implantation of an astrocyte-derived ECM for the treatment of SCI. HA is the primary component of the native CNS ECM and HA alone implantation was found to decrease CSPG staining around the lesion, and support cellular transplantation. These observations indicate that HA may be preferable to other materials for CNS injury treatment.

Practical Implications

Therapeutic Potential

Protoplasmic astrocyte ECM shows promise for treating CNS injuries.

Novel Scaffold

ECM:HA hydrogels are a novel scaffold with beneficial histologic outcomes after SCI with or without cells.

HA Preference

HA may be preferable to other materials for CNS injury treatment.

Study Limitations

1
Long-term recovery studies are required to determine if transplanted V2a interneurons functionally integrate.
2
Further experimentation is required to determine the precise nature of astrocyte phenotype change and what specific factors within the implanted ECMs might be responsible for these changes.
3
Behavioral improvements need to be assessed to see if the increased neuronal area caused by P-ECM incorporation translates into any behavioral improvements.

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