Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord

Nat Biotechnol, 2000 · DOI: 10.1038/79432 · Published: September 1, 2000

Simple Explanation

This study explores using pig cells, modified to be less likely to be rejected by the body, to repair spinal cord injuries in rats. Specifically, it looks at olfactory ensheathing cells (OECs) and Schwann cells from pigs. These cells were transplanted into rats with damaged spinal cords, and the researchers found that the cells helped the rats' nerve fibers to regrow and restore some function. This suggests that using genetically modified pig cells could be a potential way to treat spinal cord injuries in humans.

Study Duration

4-5 weeks

Participants

Adult Wistar rats

Evidence Level

Not specified

Key Findings

1
Transgenic pig OECs or Schwann cells transplantation restored impulse conduction across and beyond the lesion site in transected rat spinal cords.
2
Regenerated axons in transplanted spinal cords conducted impulses faster than normal axons.
3
Transplanted cells migrated into the denervated host tract and exhibited Schwann cell-like patterns of myelination.

Research Summary

The study investigates the potential of xenotransplantation of genetically engineered pig cells, specifically olfactory ensheathing cells (OECs) and Schwann cells expressing the human complement inhibitory protein CD59 (hCD59), to promote axonal regeneration in rat spinal cords. Results showed that transplantation of these transgenic pig cells into transected dorsal column lesions in immunosuppressed rats led to restoration of impulse conduction across the lesion site, with regenerated axons exhibiting faster conduction velocities. The findings suggest that xenotransplantation of myelin-forming cells from genetically altered pigs can induce elongative axonal regeneration and remyelination, offering a potential cell therapy approach for spinal cord repair.

Practical Implications

Potential for Human Cell Therapies

Genetically engineered pig cells could serve as a readily available source for human cell therapies, overcoming ethical and quantity limitations associated with primate tissues.

Overcoming Immune Rejection

Engineering pig cells to express human complement inhibitory proteins like hCD59 can mitigate the issue of natural antibody reactivity and complement activation, improving transplant success.

Spinal Cord Injury Treatment

The study provides a foundation for considering transgenic pig OECs and Schwann cells as candidates for xenotransplantation studies in humans with spinal cord injuries, offering a potential avenue for restoring function.

Study Limitations

1
The level of transgene expression was lower in OECs and Schwann cells compared to endogenous SLA class I expression.
2
The study was conducted in immunosuppressed rats, which may not fully represent the immune response in humans.
3
Long-term effects of the transplantation were not evaluated.

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