title: First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up.
abstract: OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Gersey
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: S Shelby
authors.initials: SS
authors.lastname: Burks
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Anderson
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Marine
authors.initials: M
authors.lastname: Dididze
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.affiliation: Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Levi
mesh_terms: D000059:Accidents; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries* / Q000601:surgery*; D020426:Sciatic Neuropathy / Q000000981:diagnostic imaging / Q000601:surgery*; D013497:Sural Nerve / Q000502:physiology / Q000637:transplantation*; D014182:Transplantation, Autologous; D014948:Wounds, Gunshot / Q000000981:diagnostic imaging / Q000601:surgery*
keywords: AGC = axon guidance channel; DN4 = Neuropathic Pain Diagnostic Questionnaire; ISO = International Organization for Standardization; MRC = Medical Research Council; SC = Schwann cell; Schwann cells; nerve injury; repair; sciatic nerve; sural nerve; transplantation