Co-overexpression of OPN, IGF-1 and CNTF augment the therapeutic effect of DPSC on spinal cord injury

Regenerative Therapy, 2023 · DOI: https://doi.org/10.1016/j.reth.2023.11.004 · Published: November 5, 2023

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) is a complex condition with limited effective treatments. This study explores using gene-modified dental pulp stem cells (DPSCs) to repair injured spinal cords by injecting them directly into the damaged area. The researchers modified DPSCs with adenovirus to carry osteopontin (OPN), Insulin-like growth factor 1 (IGF-1), and cailiary-derived neurotrophic factor (CNTF), abbreviated as Ad-OIC. These modified cells, named DPSC-OIC, were then tested for their effects on nerve cells and in SCI mice. The study found that DPSC-OIC enhanced nerve cell growth and protected them from damage. In SCI mice, DPSC-OIC improved motor function, reduced tissue damage seen in MRI scans, and promoted bladder function recovery, suggesting a novel approach to treating SCI.

Study Duration

Not specified

Participants

Mice with spinal cord injury

Evidence Level

Not specified

Key Findings

1
DPSC-OIC treatment could increase Basso-Mouse Scale (BMS) scores, improve Magnetic Resonance Imaging (MRI) manifestation and promote bladder function recovery in SCI mice.
2
DPSC-OIC treatment could attenuate cell apoptosis and promote cell proliferation in SCI mice, indicated by decreased Cleaved-Caspase-3 expression and elevated Ki-67 expression.
3
DPSC-OIC treatment upregulated neural stem cell markers (Nestin and Sox2) in SCI mice, indicating enhanced neurogenesis.

Research Summary

This study investigates the therapeutic potential of dental pulp stem cells (DPSCs) modified to overexpress osteopontin (OPN), Insulin-like growth factor 1 (IGF-1), and ciliary-derived neurotrophic factor (CNTF) (DPSC-OIC) in treating spinal cord injury (SCI). DPSC-OIC enhanced the proliferation and axon growth of HT-22 cells, protected HT-22 cells from H2O2 induced apoptosis, and survived for more than two weeks in the local injection site in SCI mice. DPSC-OIC treatment improved motor function recovery, reduced tissue damage, and promoted bladder function recovery in SCI mice, suggesting DPSC-OIC as a potential therapy for SCI.

Practical Implications

Potential SCI Therapy

DPSC-OIC could be a novel and effective method for treating SCI, offering a potential therapeutic strategy.

Enhanced Neuroprotection

Co-overexpression of OPN, IGF-1, and CNTF enhances neuroprotection and promotes neural regeneration in the injured spinal cord.

Stem Cell Modification

Gene modification of DPSCs can augment their therapeutic effect on SCI, providing a promising avenue for stem cell-based therapies.

Study Limitations

1
The study primarily focuses on the effect of DPSC-OIC on neuro cells, while the behavior of other cell types (astrocytes, oligodendrocytes, microglia) also plays an important role in SCI recovery, which warrants further investigation.
2
The study lacks long-term follow-up data on the efficacy and safety of DPSC-OIC treatment in SCI mice.
3
The clinical applicability of DPSC-OIC treatment may be limited by the challenges of cell transplantation and potential immune responses.

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