Remyelination of the nonhuman primate spinal cord by transplantation of H-transferase transgenic adult pig olfactory ensheathing cells

FASEB J., 2004 · DOI: 10.1096/fj.03-0214fje · Published: February 1, 2004

Simple Explanation

Olfactory ensheathing cells (OECs) have shown promise in rodent studies for spinal cord repair. This study investigates if OECs from transgenic pigs can promote remyelination in a primate model. The researchers transplanted highly purified OECs from transgenic pigs, modified to express the H-transferase gene (HT), into demyelinated areas of African green monkey spinal cords. The study found that OEC transplantation led to significant remyelination in the monkey spinal cord, suggesting potential for treating spinal cord injuries using this approach.

Study Duration

4-5 weeks

Participants

18 African green monkeys

Evidence Level

Not specified

Key Findings

1
Transplantation of HT transgenic pig OECs into demyelinated lesions in the monkey spinal cord resulted in robust remyelination in 62.5% of transplant sites.
2
The remyelination observed was characterized by a peripheral myelin pattern, similar to that produced by Schwann cells, and was confirmed by immunohistochemical analysis showing the presence of p75-expressing pig OECs within the remyelinated areas.
3
In vitro assays confirmed the high purity (>98%) of the transplanted OECs, the expression of the HT transgene, and a reduction in complement activation compared to non-transgenic controls.

Research Summary

This study demonstrates the potential of xenotransplantation of characterized OECs into the primate spinal cord, resulting in remyelination of demyelinated axons. The use of HT transgenic pig OECs, modified to resist humoral immunity, highlights the potential utility of transgenic porcine tissues for human cell therapy. The findings suggest that the remyelination potential observed in rodents with OEC transplantation can be extrapolated to primates, supporting the development of OEC-based therapies for spinal cord injury.

Practical Implications

Spinal Cord Injury Therapy

OEC transplantation may offer a novel therapeutic approach for promoting remyelination and functional recovery in spinal cord injuries.

Xenotransplantation Potential

Genetically modified pig OECs could serve as a readily available cell source for transplantation, overcoming limitations associated with autologous OEC harvesting.

Overcoming Immune Rejection

The use of HT transgenic OECs demonstrates a strategy for reducing immune rejection, enhancing the survival and efficacy of transplanted cells.

Study Limitations

1
Lesions in the primate spinal cord were more variable in size than similar lesions in the rodent, and the tendency for axon loss was greater in the monkey.
2
Remyelination was not observed in six transplant sites. It is believed that given the difficulty of the model related to the irregularity of the lesions that many of the negative animals were negative due to surgical difficulties in getting the cell transplants into the lesion site.
3
Not all recipients underwent blood collection and serum analysis and therefore a complete set of data are not possible.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine