The Use of Autologous Schwann Cells to Supplement Sciatic Nerve Repair with a Large Gap: First in Human Experience

Abstract

Insufficient donor nerve graft material in peripheral nerve surgery remains an obstacle for successful long-distance regeneration. Schwann cells (SCs) can be isolated from adult mammalian peripheral nerve biopsies and can be grown in culture and retain their capacity to enhance peripheral nerve regeneration within tubular repair strategies in multiple animal models. Human Schwann cells (hSCs) can be isolated, expanded in number, and retain their ability to promote regeneration and myelinate axons, but have never been tested in a clinical case of peripheral nerve injury. A sural nerve biopsy and peripheral nerve tissue from the traumatized sciatic nerve stumps was obtained after Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval as well as patient consent. The SCs were isolated after enzymatic digestion of the nerve and expanded with the use of heregulin β1 (0.1 µg/ml) and forskolin (15 mM). After two passages the Schwann cell isolates were combined with sural nerve grafts to repair a large sciatic nerve defect (7.5 cm) after a traumatic nerve injury. The sural nerve and the traumatized sciatic nerve ends both served as an excellent source of purified (90% and 97%, respectively) hSCs. Using ultrasound and magnetic resonance imaging (MRI) we were able to determine continuity of the nerve graft repair and the absence of tumor formation. The patient had evidence of proximal sensory recovery and definitive motor recovery distal to the repair in the distribution of the tibial and common peroneal nerve. The patient did experience an improvement in her pain scores over time. The goals of this approach were to determine the safety and clinical feasibility of implementing a new cellular repair strategy. In summary, this approach represents a novel strategy in the treatment of peripheral nerve injury and represents the first reported use of autologous cultured SCs after human peripheral nerve injury.

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

“…Stab wounds, gunshot wounds, and boat propeller injuries are commonly associated with midsciatic injury. 8,22 Injury location and sciatic division have been associated with differing rates of success after nerve autograft repair. High sciatic injuries involving the peroneal component have been associated with poor outcomes, whereas midthigh injuries to the tibi-al component have had higher rates of success.…”

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 .…”

“…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.…”

“…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

“…4 Various nerve growth factors-brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and nonphosphorylated neurofilament (BDNF, GDNF, and NNF)-have all been reported to potentially accelerate and improve functional recovery in both animal and human models. 6 Additional therapeutics such as electrical stimulation and transient immunosuppression with FK506 have also been successful in facilitating improved nerve regeneration and clinical outcomes.…”