Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration

Advanced Science, 2024 · DOI: 10.1002/advs.202304761 · Published: December 25, 2023

Regenerative Medicine Spinal Disorders Biomedical

Simple Explanation

This study introduces a new approach to treating intervertebral disc degeneration (IDD) using injectable hydrogel microspheres called LMGDNPs. These microspheres are designed to deliver nutrients, reduce harmful metabolic byproducts like lactate, and promote cell repair within the damaged disc. The LMGDNPs are made by combining a nanozyme (LM) that consumes lactate with glucose-enriched decellularized nucleus pulposus hydrogel microspheres (GDNPs). This combination aims to improve the survival and function of both implanted stem cells and the disc's existing cells. The microspheres were tested in vitro and in vivo, showing promising results in promoting cell survival, matrix regeneration, and activation of autophagy, a cellular process that helps remove damaged components and maintain cell health. The study suggests that LMGDNPs could be a valuable tool for stem cell therapy and endogenous repair strategies for IDD.

Study Duration

Not specified

Participants

Bovine tails, human tissues, Sprague Dawley (SD) male rats

Evidence Level

Not specified

Key Findings

1
LMGDNPs showed a delayed release of lactate oxidase (LOX) and effectively consumed lactate, a harmful metabolic byproduct, creating a more favorable environment for cells.
2
Mesenchymal stem cells (MSCs) cultured on LMGDNPs exhibited improved cell viability and showed an increased nucleus pulposus cell (NPC) phenotype, indicating enhanced differentiation towards disc cells.
3
LMGDNPs activated autophagy in NPCs by activating transforming growth factor 𝛽2 overlapping transcript 1 (TGFB2-OT1), a long noncoding RNA, which is crucial for cell survival and matrix regeneration.

Research Summary

The study developed LMGDNPs, injectable hydrogel microspheres, to address the nutrient imbalance and harsh microenvironment in degenerated intervertebral discs (IVD). LMGDNPs promoted cell survival and matrix regeneration by providing nutrients, reducing lactate levels, and activating autophagy via the TGFB2-OT1 pathway. In vivo experiments demonstrated that MSCs-loaded LMGDNPs preserved disc hydration and alleviated matrix degradation, suggesting their potential as a delivery system for stem cell therapy and endogenous repair.

Practical Implications

Improved Stem Cell Therapy

LMGDNPs can enhance the survival and efficacy of stem cells implanted in degenerated discs by addressing the nutrient deficiency and toxic metabolic environment.

Endogenous Disc Repair

The microspheres can promote the repair of existing disc cells by reducing lactate accumulation and stimulating autophagy, leading to matrix regeneration.

Clinical Translation Potential

The injectable nature, ease of production, and promising in vivo results suggest that LMGDNPs have the potential to be translated into a clinically viable treatment for intervertebral disc degeneration.

Study Limitations

1
The study relies on bovine and rat models, and further research is needed to confirm the results in human clinical trials.
2
The long-term effects of LMGDNP implantation on disc regeneration and stability were not fully evaluated.
3
The specific mechanisms by which LMGDNPs interact with the immune system and affect inflammation in the disc were not thoroughly investigated.

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