Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

Scientific Reports, 2019 · DOI: 10.1038/s41598-019-50367-x · Published: September 6, 2019

Regenerative Medicine Immunology Biomedical

Simple Explanation

Spinal cord injury (SCI) leads to chronic inflammation, hindering regeneration. This study explores using stem cells from dental apical papilla (SCAP) delivered via extracellular matrix (ECM) hydrogels to reduce inflammation after SCI. The researchers tested bone and spinal cord derived ECM hydrogels for their ability to deliver SCAP and modulate inflammatory responses in microglial cells, which are key players in SCI-related inflammation. The study found that ECM hydrogels can effectively deliver SCAP, preserving their viability and immunomodulatory capacity, suggesting a potential therapeutic strategy for mitigating inflammation and promoting regeneration after SCI.

Study Duration

Not specified

Participants

Bovine tibiae, porcine spinal cords, human SCAP (RP89 cell line), mouse brain microglial cells (BV2 cells)

Evidence Level

Not specified

Key Findings

1
ECM hydrogels, particularly in solubilized form, can modulate inflammation in LPS-stimulated microglial cells, with spinal cord-derived hydrogels reducing the Nos2/Arg1 ratio and bone-derived hydrogels reducing Tnf expression.
2
SCAP encapsulation within ECM hydrogels does not impede their immunomodulatory properties, with significant downregulation of the Nos2/Arg1 ratio observed for all SCAP-embedded hydrogels.
3
Bone ECM hydrogels, either alone or with SCAP, significantly reduced Tnf expression, indicating a potential synergistic effect in mitigating inflammation.

Research Summary

This study investigates the potential of ECM hydrogels to deliver SCAP for reducing inflammation after spinal cord injury. The researchers evaluated the mechanical properties of bone and spinal cord derived ECM hydrogels and their impact on inflammatory responses in microglial cells. The findings demonstrate that ECM hydrogels are suitable vehicles for SCAP delivery, preserving their viability and immunomodulatory capacity. Solubilized forms of ECM hydrogels modulated inflammation in LPS-stimulated microglia, with spinal cord-derived hydrogels reducing the Nos2/Arg1 ratio and bone-derived hydrogels reducing Tnf expression. Encapsulation of SCAP within ECM hydrogels did not impede their ability to mitigate inflammation, suggesting a potential therapeutic strategy for promoting regeneration after SCI. The study concludes that ECM hydrogels are promising materials for delivering SCAP to the injured spinal cord, due to their physical properties, SCAP viability preservation, and immunomodulatory capacity.

Practical Implications

Therapeutic Delivery System

ECM hydrogels could be used as a delivery system for stem cells to treat spinal cord injuries.

Immunomodulatory Potential

Harnessing the immunomodulatory properties of ECM hydrogels and SCAP for SCI therapy may improve recovery outcomes.

Tissue-Specific Hydrogel Selection

The selection of ECM hydrogel source (bone or spinal cord) may be tailored to specific therapeutic goals based on their differential impacts on inflammatory markers.

Study Limitations

1
Further investigation of the biochemical profiles of the tissue-specific hydrogels is required to elucidate the mechanisms by which SCAP and hydrogels modulate inflammation.
2
Omics analyses are needed to explore the immediate impact of ECM hydrogel composition upon SCAP secretome and downstream regulation of inflammation.
3
The study is limited to in vitro experiments and further in vivo studies are required to validate these findings.

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