gms | German Medical Science

Objectives/Interrogation: Incomplete nerve regeneration after injuries to the peripheral nervous system remains a significant problem in clinical routine and raises the need for supportive strategies. We examined the effect of an additional adipose derived progenitor cell-loaded fibrin glue conduit in the model of a 20 mm long peripheral nerve defect in the rat treated with an autologous nerve transplant.

Methods: Cells were isolated from the inguinal fat pad of the rats using the ARC centrifuge (Ingeneron). To improve the regenerative potential of adipose derived progenitor cells, we preconditioned the cells in 2% of hypoxia for 3 days before they were applied. Cells were suspended in liquid fibrin glue (ARTISS; Baxter) which was then cast into a solid nerve conduit of 25 mm in length and 2 mm of wall thickness. The cell-containing conduits were then applied around a 20 mm autologous nerve graft in a sciatic nerve defect model covering both coaptation sites. While the experimental group (n=9) received hypoxically preconditioned cells, the control groups received either the fibrin conduit alone (n=9), the conduit containing non-preconditioned adipose derived progenitor cells (n=9) or no conduit at all (n=9).

During the trial period of 16 weeks we conducted weekly walking-track and static foot-print-analyses. Afterwards the animals were sacrificed and the bilateral gastrocnemius muscle was weighed. Histological evaluation including axon density and axon size was carried out.

Results and Conclusions: Functional analysis in terms of sciatic function index showed significant improvement in all groups treated additionally with fibrin conduits when compared to the control group that did neither receive conduit nor cells indicating faster functional regeneration. The group that received hypoxically preconditioned cells produced the best results, followed by the non-preconditioning group, which in turn yielded better results than the fibrin conduit group without cells.

The gastrocnemius muscle's weight was significantly higher in conduit groups and conduit-treated animals showed an increased axon density when compared to control group without conduit. Slightly higher numbers of axons in animals with cell-containing conduits were detected.

These results indicate the beneficial effect of an adipose derived progenitor cell-loaded fibrin glue nerve conduit in addition to microsurgical nerve repair in the model of an autologous nerve transplant in the rat, yet the underlying mechanisms need to be further investigated.