BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury

The Journal of Neuroscience, 2009 · DOI: 10.1523/JNEUROSCI.2769-09.2009 · Published: November 25, 2009

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the potential of using human mesenchymal stem cells (hMSCs) to treat spinal cord injury (SCI) in rats. The researchers transplanted hMSCs, some modified to secrete brain-derived neurotrophic factor (BDNF-hMSCs), into rats with SCI to assess their impact on functional recovery. The study found that rats receiving BDNF-hMSCs showed improved locomotor recovery compared to those receiving unmodified hMSCs. This suggests that BDNF plays a crucial role in the therapeutic effects of hMSCs. The researchers also observed increased sprouting of nerve fibers and improved survival of nerve cells in the brain and spinal cord of rats treated with BDNF-hMSCs, indicating structural changes associated with functional improvement.

Study Duration

5 weeks

Participants

Adult female Sprague Dawley rats (n = 66)

Evidence Level

Level II; Experimental study

Key Findings

1
Transplantation of BDNF-hMSCs resulted in improved locomotor recovery compared to hMSC transplantation alone.
2
Both hMSC and BDNF-hMSC transplants promoted sprouting of corticospinal tract (CST) fibers, with BDNF-hMSCs showing greater sprouting, especially in the dorsal funiculus caudal to the injury site.
3
Transplantation of BDNF-hMSCs led to increased 5-HT fiber immunoreactivity in the ventral horn caudal to the lesion, indicating increased serotonergic innervation.

Research Summary

This study evaluated the therapeutic potential of human mesenchymal stem cells (hMSCs) and brain-derived neurotrophic factor-secreting hMSCs (BDNF-hMSCs) in a rat model of spinal cord injury (SCI). The results indicated that BDNF-hMSC transplantation led to improved locomotor recovery, increased axonal sprouting, and enhanced survival of corticospinal neurons compared to hMSC transplantation alone. These findings suggest that cellular delivery of BDNF by hMSCs can positively impact functional outcome in SCI by promoting structural changes in the brain and spinal cord.

Practical Implications

Therapeutic Potential

BDNF-hypersecreting hMSCs show promise as a therapeutic intervention for acute spinal cord injury.

Mechanism of Action

The study elucidates the role of BDNF in mediating the beneficial effects of hMSC transplantation, highlighting its neuroprotective and axon growth-promoting properties.

Future Research

Further investigation is warranted to optimize BDNF delivery methods and explore the long-term effects of BDNF-hMSC transplantation in SCI.

Study Limitations

1
The study was conducted in a rat model, and the results may not be directly applicable to humans.
2
The study focused on acute SCI, and the long-term effects of hMSC transplantation remain to be investigated.
3
The precise mechanisms underlying the observed axonal sprouting and neuroprotection require further elucidation.

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