AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

Cell Death & Disease, 2021 · DOI: 10.1038/s41419-021-03546-6 · Published: March 26, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores a new approach to treat spinal cord injury (SCI) by using neural stem cells (NSCs) modified to produce a growth factor called bFGF. The NSCs were engineered to produce bFGF specifically in low-oxygen conditions, which are common in SCI, to promote nerve repair. The modified NSCs were transplanted into rats with SCI, and the results showed improved functional recovery compared to control groups.

Study Duration

60 days

Participants

Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
AAV2-5HRE-bFGF-NSCs treatment yielded temporally increased expression of bFGF in SCI.
2
Treatment with AAV2-5HRE-bFGF-NSCs improved scores of functional recovery after SCI compared to vehicle control.
3
AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy.

Research Summary

This study investigates the therapeutic potential of neural stem cells (NSCs) modified with adeno-associated virus 2 (AAV2) to express basic fibroblast growth factor (bFGF) under the control of a hypoxia response element (HRE) for the treatment of spinal cord injury (SCI) in rats. The results demonstrated that transplantation of AAV2-5HRE-bFGF-NSCs led to improved functional recovery in SCI rats, accompanied by increased nerve regeneration and reduced glial scar formation and cell autophagy. The findings suggest that AAV2-5HRE-bFGF-NSCs may be a promising therapeutic strategy for SCI repair, warranting further investigation for clinical translation.

Practical Implications

Clinical Translation

This study provides preclinical data supporting the potential use of AAV2-5HRE-bFGF-NSCs in future clinical trials for SCI repair.

Hypoxia-Targeted Therapy

The use of hypoxia response elements (HRE) to regulate bFGF expression offers a targeted approach to address the challenging hypoxic environment in SCI.

Autophagy Modulation

The finding that AAV2-5HRE-bFGF-NSCs inhibit SCI-induced autophagy suggests a potential mechanism for promoting nerve regeneration and functional recovery.

Study Limitations

1
The study was conducted on rats, and further research is needed to confirm these findings in larger animal models and eventually in humans.
2
The long-term effects of AAV2-5HRE-bFGF-NSCs transplantation on SCI repair require further investigation.
3
The precise mechanisms by which AAV2-5HRE-bFGF-NSCs modulate autophagy and promote nerve regeneration warrant further exploration.

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