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.