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

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.

Ensheathing Cells and Methylprednisolone Promote Axonal Regeneration and Functional Recovery in the Lesioned Adult Rat Spinal Cord

“…Investigators have examined previously the ability of ECs to promote axonal regeneration after SCI (Li et al, 1997(Li et al, , 1998Imaizumi et al, 2000;Ramon-Cueto et al, 2000;Lu et al, 2001). Our results support data that has been reported previously regarding the ability of ECs to promote axonal regeneration and functional recovery.…”

“…Pig ECs had been genetically engineered to express a human complement inhibitory protein, which is intended to decrease rejection of the tissue if transplanted into human beings (Imaizumi et al, 2000). After transplantation into adult rats after dorsal column transection, pig EC transplants promoted axonal regeneration, elongation, and remyelination and restored impulse conduction across the lesion site (Imaizumi et al, 2000).…”

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells

“…Furthermore, preservation of even a small percentage of tissue significantly enhances functional recovery (7). Although there have been encouraging reports of deficit reduction (8)(9)(10) and axonal regrowth by blocking inhibitory molecules and antagonizing secondary injury mechanisms (11); myelin replacement by stem (12), Schwann (13), and olfactory ensheathing cells (14,15); delivery of growth factors (16)(17)(18) and small molecules (19); and implantation of fetal tissue (19) and scaffolds (20)(21)(22)(23), as yet there is no practical treatment for SCI.…”

The contribution of farm animals to human health

“…Further examples for the potential use of porcine neural cells are in cases of stroke and focal epilepsy [54]. Olfactory ensheathing cells (OECs) or Schwann cells derived from hCD59 transgenic pigs promoted axonal regeneration in rat spinal cord lesion [55]. Thus, cells from genetically modified pigs could restore electrophysiologically functional axons across the site of a spinal cord transsection.…”