Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration

Journal of Tissue Engineering, 2020 · DOI: 10.1177/2041731420980136 · Published: November 21, 2020

Regenerative Medicine Neurology Biomedical

Simple Explanation

This study investigates the combined effects of a flavonoid small molecule, 7, 8-dihydroxyflavone (DHF), and bone marrow-derived stem/stromal cells (BMSCs) in acellular nerve allografts (ANAs) to promote sciatic nerve regeneration. The researchers found that 7, 8-DHF increases the levels of a receptor called TrkB and its downstream signaling molecule ERK1/2. This promotes the proliferation, survival, and differentiation of BMSCs into Schwann-like cells, which are important for nerve regeneration. In animal models, the combination of 7, 8-DHF and BMSCs improved nerve regeneration, muscle function, and motor recovery after sciatic nerve injury, suggesting a potential therapeutic approach.

Study Duration

42 days

Participants

60 C57BL6 mice and 24 adult female CD1 (ICR) mice

Evidence Level

Not specified

Key Findings

1
7, 8-DHF promotes the proliferation, survival, and Schwann-like cell differentiation of BMSCs in vitro by upregulating TrkB and ERK1/2 phosphorylation.
2
In vivo, 7, 8-DHF promotes the survival of transplanted BMSCs and enhances axonal growth and myelination in regenerating ANAs.
3
The combination of 7, 8-DHF and BMSCs significantly upregulates TrkB and ERK1/2 phosphorylation expression in regenerating ANAs and increases TrkB expression in the lumbar spinal cord.

Research Summary

This study investigates the combined effects of 7, 8-dihydroxyflavone (DHF) treatment and bone marrow-derived stem/stromal cells (BMSCs) engraftment into acellular nerve allografts (ANAs) for promoting sciatic nerve regeneration. The key findings demonstrate that 7, 8-DHF promotes BMSC proliferation, survival, and differentiation into Schwann-like cells in vitro, and enhances axonal growth and myelination in vivo. The combined treatment significantly improved motor functional recovery, upregulated TrkB and ERK1/2 phosphorylation, and increased TrkB expression in the lumbar spinal cord, indicating a potential therapeutic approach for peripheral nerve injury.

Practical Implications

Peripheral Nerve Injury Treatment

The combination of 7, 8-DHF and BMSCs shows promise as a therapeutic strategy for promoting nerve regeneration and functional recovery after peripheral nerve injury.

BMSC Enhancement

7, 8-DHF can enhance the therapeutic potential of BMSCs by promoting their survival, proliferation, and differentiation into Schwann-like cells.

TrkB Signaling

Targeting the TrkB signaling pathway with small molecules like 7, 8-DHF may offer a novel approach to stimulate nerve regeneration and improve outcomes after nerve graft transplantation.

Study Limitations

1
The study did not elucidate the long-term functional recovery role of the combined treatment in vivo after PNI.
2
The exact cellular and molecular mechanisms by which the benefits are observed are not fully understood.
3
The study is limited to a specific animal model (mice), and results may not be directly transferable to humans.

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