A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration

Cells, 2023 · DOI: 10.3390/cells12172161 · Published: August 28, 2023

Spinal Disorders Regenerative Medicine & Stem Cells

Simple Explanation

Intervertebral disc degeneration (IDD) is a common cause of back pain, and current treatments often have limitations. Therefore, regenerative treatments are needed. Mesenchymal stem cell (MSC) therapy is a promising approach, as MSCs can reduce inflammation, prevent cell death, promote the production of extracellular components, and differentiate into IVD cells. Researchers are exploring various molecules, scaffolds, and environmental factors that can help MSCs differentiate into IVD cells. These factors can be used to create refined protocols for MSC differentiation, offering multiple therapeutic options for IDD. Healthy nucleus pulposus (NP) cells (NPCs) and NPC-derived exosomes are also being investigated for their ability to regenerate the NP and differentiate MSCs into NPC-like phenotypes. Allogeneic MSCs from cell banks could be a stable and economical source of IVD cells for differentiation.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
TGF-β superfamily members and GDF5 and 6 played key roles in MSC differentiation into NPC-like cells, with BMP-7 and GDF6 being potentially the most effective.
2
Direct treatment of BMSCs with NPC exosomes was more effective than trans-well co-culture, suggesting purified exosomes with high yield are more inductive of MSC differentiation than generally used co-culture.
3
Strategies to precondition MSCs before implantation, such as overexpressing HIF-1α or BCL2, may promote cell survival in the harsh environment of the degenerated NP.

Research Summary

This review comprehensively examines methodologies to induce the differentiation of MSCs into IVD cells for regenerative therapies for IDD, focusing on molecules, scaffolds, and environmental factors. The study highlights the potential of MSC therapy for IDD due to its ability to regenerate cells and tissues, underscoring the importance of further research to identify novel and efficient differentiation methodologies. It discusses various factors, including growth factors, endogenous molecules, exogenous factors, cellular engineering, conditioned mediums, exosomes, co-cultures, biomaterials, and environmental factors, that influence MSC differentiation.

Practical Implications

Enhanced MSC Differentiation Protocols

Combining molecules, biomaterials, and environmental factors can create novel methodologies for MSC differentiation into IVD cells.

Clinical Translation of MSC Therapies

Further research should focus on the cost-effectiveness and biocompatibility of biomaterials to facilitate clinical application of MSC-based regenerative medicine for IDD.

Preconditioning Strategies for MSC Survival

Preconditioning MSCs, such as overexpressing HIF-1α or BCL2, can improve cell survival in the harsh environment of degenerated intervertebral discs, enhancing treatment outcomes.

Study Limitations

1
Lack of comprehensive studies on interactions between different endogenous and exogenous molecular factors, limiting clinical use.
2
Potential foreign body reactions with synthetic and chimeric biomaterials.
3
Uncertainty regarding long-term viability of implanted MSCs.

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