Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

Abstract

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up

“…1,6,7,9,11,12,16,17,27,28,34,37,38,[40][41][42]44 Berrocal et al demonstrated that adding autologous SCs suspended in serum to AGCs significantly enhanced the ability to bridge larger gap distances in sciatic nerve repair in rats. 3 Autologous SCs can be harvested from either a donor nerve or from the epicenter of the traumatized nerve ends in sharp injuries (propeller injury, gunshot wound, stab wound). Harvesting SCs from donor nerves requires sacrifice of sensory donor nerves, which may lead to future morbidity, whereas harvesting from the traumatized nerve ends will lead to no deficit because these ends will eventually scar and be sacrificed by the surgeon.…”

“…10,14,15,19,21,23,24,30,31 After this foundation was laid, several studies have shown the ability of SCs to enhance axonal regeneration and improve functional recovery in peripheral nerve injury in mice, rats, and nonhuman primates. 3,20,24,25,34 In this report we present 2 long-segment (7.5-and 5-cm) sciatic nerve injuries where SCs were combined with an autologous nerve construct. These are the first 2 cases in which autologous SCs were transplanted into peripheral nerve injuries in humans (Table 1).…”

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

“…The rate of axon regeneration across 15 mm rat sciatic nerve gaps is faster if macrophages with a pro-healing (M2a and M2c phenotype) vs. pro-inflammatory phenotype are combined with polymeric nerve tubes [329]. This can be accomplished by the local delivery of either Interferon-gamma (IFN-gamma) or Interleukin-4 (IL-4), within the tubes [329].…”

“…This can be accomplished by the local delivery of either Interferon-gamma (IFN-gamma) or Interleukin-4 (IL-4), within the tubes [329]. The neuron-macrophage interactions involved in eliciting a pro-regenerative phenotype in macrophages may be a novel target to induce long-lasting regenerative processes after axonal injuries in the CNS [327].…”

Challenges in sciatic nerve repair: anatomical considerations

“…2,13 In addition to restoring motor and/or sensory function, nerve repair can mitigate and/or reduce the incidence and severity of neuroma formation and subsequent development of neuropathic pain. 5 With recent advances in surgical technique and the use of tendon transfers, patients can expect better functional outcomes than ever before. 2 When the damage to the sciatic nerve is extensive enough to preclude coaptation, nerve grafting techniques with autologous sensory nerve graft are used.…”