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

Nature Biotechnology volume 18, pages 949–953 (2000)Cite this article

Abstract

Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord.

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Figure 1: FACS analysis of transgenic Schwann cells and transgenic olfactory ensheathing cells (OECs) expressing CD59.
Figure 2: Conduction across the transplantation zone.
Figure 3: Conduction properties of transplant-induced regenerated spinal cord axons.
Figure 4: Presence of transgenic pig donor OECs in the recipient spinal cord.
Figure 5: Ultrastructural characteristics of regenerated axons following transgenic pig OEC and Schwann cells transplantation.

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Acknowledgements

This work was supported in part by an Advanced Technology Program grant from the National Institutes of Standards and Technology to W.L.F, the National Institutes of Health (NIH) (NS 10174); the National Multiple Sclerosis Society (RG2135) and the Medical Research and Rehabilitation and Development Research Services of the Department of Veterans Affairs.

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Authors and Affiliations

  1. Department of Neurology, Yale University School of Medicine, New Haven, 06510, CT

    Toshio Imaizumi, Karen L. Lankford & Jeffery D. Kocsis

  2. Department of Veterans Affairs Medical Center, Neuroscience Research Center, West Haven, 06516 , CT

    Toshio Imaizumi, Karen L. Lankford & Jeffery D. Kocsis

  3. Alexion Pharmaceuticals, Inc, 25 Science Park, New Haven, 06511, CT

    Willis V. Burton & William L. Fodor

Authors
  1. Toshio Imaizumi
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  2. Karen L. Lankford
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  3. Willis V. Burton
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  4. William L. Fodor
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  5. Jeffery D. Kocsis
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Correspondence to Jeffery D. Kocsis.

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Imaizumi, T., Lankford, K., Burton, W. et al. Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord. Nat Biotechnol 18, 949–953 (2000). https://doi.org/10.1038/79432

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