Low‑intensity pulsed ultrasound promotes mesenchymal stem cell transplantation‑based articular cartilage regeneration via inhibiting the TNF signaling pathway

Stem Cell Research & Therapy, 2023 · DOI: https://doi.org/10.1186/s13287-023-03296-6 · Published: March 22, 2023

Simple Explanation

Articular cartilage, providing a smooth surface and decreasing friction for articulation, suffers great pressure during the frequent daily joint movement and tends to gradually wear away or suddenly get injured. Mesenchymal stem cells (MSCs) have the advantages of rich sources, strong proliferative and self-renewal ability, and multi-lineage differentiation ability including chondrogenic differentiation, making them an ideal cell type for cell transplantation-based cartilage tissue repair. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound delivered at an intensity lower than 3 W/cm2 and transmitted through and into tissues as pulsed acoustic pressure waves; it removes the thermal component at higher intensities and primarily provides mechanical stimulation.

Study Duration

6 weeks (in vivo)

Participants

24 male SD rats (10 weeks old)

Evidence Level

Not specified

Key Findings

1
LIPUS stimulation effectively promoted the expression of mature cartilage-related genes and proteins and inhibited TNF-α gene expression in hUC-MSCs.
2
LIPUS stimulation exhibited anti-inflammation in C28/I2 cells.
3
The articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation.

Research Summary

This study explored the effects of LIPUS stimulation on chondrogenic differentiation of hUC-MSCs, proliferation, and anti-inflammation of human chondrocyte C28/I2 cells. Rat knee articular cartilage defect models were established to verify LIPUS- and hUC-MSC-based cartilage regeneration in vivo. The present study validated in vivo experiments in injured articular cartilage rat models and proposed a new possible regenerative mechanism related to LIPUS-induced TNF signaling pathway inhibition.

Practical Implications

Clinical Value for Osteoarthritis Relief

LIPUS stimulation with hUC-MSC transplantation shows clinical value for articular cartilage regeneration and potential relief of osteoarthritis.

Therapeutic Potential

LIPUS demonstrates therapeutic potential in treating articular cartilage injury and promoting hUC-MSCs transplantation-based cartilage regeneration treatment.

Anti-inflammatory Applications

The anti-inflammatory effect of LIPUS suggests its use for OA treatment and promoting a favorable microenvironment for newly differentiated chondrocytes.

Study Limitations

1
The ultrasound transducers convey plane waves but not focused waves.
2
The impact of other LIPUS parameters including central frequency and duty cycle was not studied.
3
Only the TNF signal pathway was studied, among differential gene pathways following LIPUS stimulation.

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