A Guidance Channel Seeded With Autologous Schwann Cells for Repair of Cauda Equina Injury in a Primate Model

Abstract

Background/Objective: To evaluate an implantable guidance channel (GC) seeded with autologous Schwann cells to promote regeneration of transected spinal nerve root axons in a primate model. Methods: Schwann cells were obtained from sural nerve segments of monkeys (Macaca fascicularis; cynomolgus). Cells were cultured, purified, and seeded into a PAN/PVC GC. Approximately 3 weeks later, monkeys underwent laminectomy and dural opening. Nerve roots of the L4 through L7 segments were identified visually. The threshold voltage needed to elicit hindlimb muscle electromyography (EMG) after stimulation of intact nerve roots was determined. Segments of 2 or 3 nerve roots (each ;8-15 mm in length) were excised. The GC containing Schwann cells was implanted between the proximal and distal stumps of these nerve roots and attached to the stumps with suture. Follow-up evaluation was conducted on 3 animals, with survival times of 9 to 14 months. Results: Upon reexposure of the implant site, subdural nerve root adhesions were noted in all 3 animals. Several of the implanted GC had collapsed and were characterized by thin strands of connective tissue attached to either end. In contrast, 3 of the 8 implanted GC were intact and had white, glossy cables entering and exiting the conduits. Electrical stimulation of the tissue cable in each of these 3 cases led to low-threshold evoked EMG responses, suggesting that muscles had been reinnervated by axons regenerating through the repair site and into the distal nerve stump. During harvesting of the GC implant, sharp transection led to spontaneous EMG in the same 3 roots showing a low threshold to electrical stimulation, whereas no EMG was seen when harvesting nerve roots with high thresholds to elicit EMG. Histology confirmed large numbers of myelinated axons at the midpoint of 2 GC judged to have reinnervated target muscles. Conclusions: We found a modest rate of successful regeneration and muscle reinnervation after treatment of nerve root transection with a Schwann cell-seeded, implanted synthetic GC. Newer treatments, which include the use of absorbable polymers, neurotrophins, and antiscar agents, may further improve spinal nerve regeneration for repair of cauda equina injury.

Topography, Cell Response, and Nerve Regeneration

“…A variety of strategies have been explored, including delivery of neuroprotective agents (100), addition of exogenous growth factors (101), reducing inhibitory myelin-associated factors (102), blocking the Nogo-A signaling pathway (103), promotion of a more embryonic neuronal or ECM state (104), and cell transplantation (105,106). Repair of PNS injuries has come further clinically, as small defects may currently be treated with autografts or with polymeric nerve guidance tubes (107), but large injuries still provide a significant clinical challenge (108).…”

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell—Seeded collagen foam

“…In this last study, implantation of autologous Schwann cells within an acrylonitrile vinyl chloride copolymer guidance channel yielded positive stimulus‐evoked electromyography results and regrowth across the injury site in 3 of 8 nerve roots . However, guidance channel collapse was observed with equal frequency . Indeed, surgical implantation constraints and channel collapse led us to abandon the guidance channel approach in the rat cauda equina in earlier experiments (data not shown).…”

Single-Walled Carbon Nanotubes Chemically Functionalized with Polyethylene Glycol Promote Tissue Repair in a Rat Model of Spinal Cord Injury

“…Guidance channels or bioengineered scaffolds (i.e., fibrin or hydrogel) have previously been evaluated in rodent in vivo models of SCI with encouraging, albeit incomplete, success (Calancie et al, 2009;Johnson et al, 2010a;Oudega et al, 2001;Potter et al, 2008;Xu et al, 1995). An additional approach is to enhance the scaffold characteristics by the addition of growthpromoting cells, proteins, or drugs.…”