Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

Abstract

Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Na v 1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization.

Perspectives in regeneration and tissue engineering of peripheral nerves

“…OECs, which guide the continuously regenerating axons of the olfactory neuroepithelium towards the olfactory bulb, have shown to retain a higher migratory potential and ability to penetrate glial scars in comparison to SCs (Franklin and Barnett, 1997), a property which makes them a rational trans-plantation candidate for nerve reconstruction. The employment of OEC transplantation in injured peripheral nerves have shown that, in rodents, these cells can provide trophic support, form cel-lular bridges across the site of injury, and significantly promote axonal regeneration (Verdú et al, 1999;Guntinas-Lichius et al, 2001;Radtke et al, 2005Radtke et al, , 2010Dombrowski et al, 2006).…”

“…Transplantation of OECs (Radtke et al, 2005;Dombrowski et al, 2006) into the regenerating sciatic nerve of rodents showed that OECs survived, distributed longitudinally across the lesion site and were integrated into the repaired nerves, contributing to the myelin formation of regenerated axons. These authors hypothe-sized that, after lesion, transplanted OECs are primed to produce neurotrophins and, therefore, can have an immediate effect on the injured axons before scar formation occurs.…”

Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury

“…Choi and Raisman demonstrated that the rate of eye closure increased after OEC transplantation in a facial nerve lesion model but that aberrant nerve branching was unchanged [75]. Schwann cells [76] and OECs [77] transplanted into transected sciatic nerve integrate into the injury site and form peripheral myelin on the regenerated axons. Moreover, the nodes of Ranvier of the regenerated axons myelinated by the transplanted cells express the appropriate sodium channel (Na v 1.6).…”

“…Moreover, the nodes of Ranvier of the regenerated axons myelinated by the transplanted cells express the appropriate sodium channel (Na v 1.6). Whether these engrafted cells accelerate or improve functional outcome after nerve injury is yet to be determined [77].…”

Olfactory ensheathing cell transplantation for a patient with chronic sciatic nerve injury

“…Some preclinical studies report that transplantation of olfactory ensheathing cells (OECs) for peripheral nerve injury in acute phase enhanced peripheral nerve restoration. [5][6][7][8][9] Currently, there are no reports about clinical studies on OEC for restoring chronic peripheral nerve injury. Herein, we report the case of one patient with chronic sciatic nerve injury who received OEC therapy and showed neurological functional improvement.…”