Autologous schwann cells drive regeneration through a 6-cm autogenous venous nerve conduit

Peripheral nerve regeneration is a complex series of events, involving bi-d irectional interactions between regenerating axons and Schwann cells. These authors have demonstrated in their laboratory that nerves will regenerate through a 3-cm autogenous venous nerve conduit (AVNC) in an animal model an d, with Dr. David Chiu, a similar distance in the human. They have shown th at the upper limit of nerve regeneration in an empty AVNC was 3 cm, with no evidence of nerve growth at the 6-cm mark (no-growth model). Most recently , they have demonstrated rapid growth at 1 month in a 3-cm AVNC filled with Schwann cells, compared to poor-to-no-regrowth at 1 month in controls. Whi le, in theory, Schwann-cell-derived growth factor should be sufficient to s upplant the requirement for Schwann cells, in practice, therapies with grow th factors have failed in clinical trials, with some resulting in severe mo rbidity and mortality for the subjects. The present study showed excellent nerve regeneration through a 6-cm AVNC with the addition of autologous, Sch wann cells, breaking the barrier in the previous no-growth model. In the fi rst stage, autologous Schwann cells were harvested from the contralateral p eroneal nerve of the rabbit and expanded in culture. The Schwann cells were purified to >99 percent homogeneity using differential adhesion and antibo dy-compliment-mediated cytolysis. In the second stage, 6 cm of gluteal vein were harvested and used as a conduit that was filled with either Matrigel or a slurry of Matrigel and 10(6)/ml autologous Schwann cells (n=6 control and 6 experimental animals). The non-donor side peroneal was exposed and tr ansected, leaving a gap of 6 cm. The filled gluteal vein graft (AVNC) was t hen anastomosed to the proximal and distal peroneal nerve stumps, and the r abbits were allowed to recover. Four months postoperatively, the animals we re subjected to transcardiac perfusion with EM grade fixative. The grafts w ere analyzed at the light and electronmicroscopic levels, and showed excell ent growth of nerve at 6 cm, the distal end of the AVNC.