Abstract
The bridges constructed of rat Schwann cells promote axonal regeneration across injury areas in adult rat spinal cord. Human Schwann cell constructs are effective in promoting axonal regeneration in the rat as well. In combination with rat Schwann cell transplants, infusion of the neurotrophins, brain-derived neurotrophic factor, and neurotrophin-3 into the graft or the administration of a neuroprotective agent, methylprednisolone, improve the regenerative response, including the initiation of axonal regeneration from distant brain stem neurons. When Schwann cells, genetically modified to secrete human brain-derived neurotrophic factor, are transplanted into a complete transection site and as a trail in the distal spinal cord beyond, axons grow across the transection site and along the Schwann cell trail. Schwann cells grafted into the spinal cord promote axonal regeneration in animal models; human Schwann cells have been harvested and shown to be as effective as rodent cells in transplantation experiments; and axonal regeneration, especially from distant supraspinal nuclei, can be augmented by neurotrophic factors and neuroprotection. Combinations of these experimental approaches, along with the use of inhibitor-blocking antibodies or other factors, all seem readily amenable to clinical application. Another distinct advantage of therapies using Schwann cells is that they may be obtained from a peripheral nerve biopsy from a person with spinal cord injury, and expanded to adequate numbers in culture for autotransplantation to the area of injury. Schwann cells may be genetically modified during the culture period. This is an advantage shared with engineered fibroblasts, but implanted Schwann cells may perform additional functions such as myelination.