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

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.</jats:p></jats:sec>

Evidence for cell‐contact factor involvement in neurite outgrowth of dorsal root ganglion neurons stimulated by Schwann cells

“…Although PNS axons can regenerate, clinical outcomes after injury are devastating, especially in proximal and defective injuries (Evans, Midha, & Mackinnon, ; Lundborg, ; Seddon, ; Seddon, ). Schwann cells play an important role in axonal regeneration (Jessen & Arthur‐Farraj, ), and implantation of SCs has already been tested in the clinic (Gersey et al., ). To develop a new therapy to enhance axonal regeneration in the PNS, the detailed molecular mechanisms of SC–axon interaction need to be elucidated.…”

Stem‐cell–based therapies to enhance peripheral nerve regeneration

“…The literature is also limited by the lack of data on the clinical safety and efficacy of stem cell–derived therapies, with no long‐term reports currently available. The clinical use and early promise of autologous SC therapies in clinical nerve repair suggest that cell types that can be readily pre‐differentiated in vitro to SCs (such as SKPs) or demonstrate transdifferentiation to SCs in vivo (such as BMSCs and ADSCs) may have the highest potential for clinical success. Levi and colleagues from the University of Miami recently detailed the first‐in‐human use of autologous SCs to supplement sciatic nerve repair .…”

“…In these groundbreaking studies, two patients were enrolled in a US Food and Drug Administration–approved trial to assess both the safety and ability of autologous cultured SCs to enhance regeneration through sural nerve autografts. Long‐term follow‐up in both patients demonstrated nerve graft patency, absence of tumor formation, and significant improvements in both sensory and motor impairments compared with preoperative values …”

“…152 The literature is also limited by the lack of data on the clinical safety and efficacy of stem cellderived therapies, with no long-term reports currently available. The clinical use and early promise of autologous SC therapies in clinical nerve repair 153,154 suggest that cell types that can be readily pre- Although these initial clinical studies are encouraging, more rigorous studies examining stem cell stability, differentiation, and migration patterns are required before clinical safety is definitively established. 155 Metrics that accurately characterize the clinical efficacy of stem cell-based therapies must also be identified.…”

Editorial: Autologous Schwann cells

“…1 Although only 2 cases are presented, this report not only has tremendous implications for lower-extremity sciatic injuries as described by the authors, but also has potential applications to all primary nerve repairs. Augmenting functional outcomes beyond traditional microsurgical repair strategies remains at the forefront of peripheral nerve research.…”