The Impact of Adipose-Derived Stem Cells and FK506 in Peripheral Nerve Regeneration. A Pilot Study in a Rat Model
Panayiotis D Megaloikonomos, MD1; Georgios N Panagopoulos, MD1; Andreas F Mavrogenis, MD1; Myrto Bami, MD2; Mandy Mylonaki, MD2; Georgios D Agrogiannis, MD1; Evanthia A Mitsiokapa, MD2; Elizabeth O Johnson, MD1; Panayiotis J Papagelopoulos, MD1; Panayotis N Soukakos, MD2
1Athens University Medical School, Athens, Greece, 2Orhopaedic Rescearch and Education Center OREC, Athens, Greece
Introduction: Peripheral nerve lesions often require bridging of the nerve defect. The application of a nerve autograft is the treatment of choice, but the sacrification of a functional nerve is demanded. Nerve conduits enhanced with cells or neurotrophic factors are alternatives that aim to create a favorable environment for nerve regeneration. The aim of this study was the in vivo assessment of the impact of undifferentiated adipose-derived stem cells and FK506 (tacrolimus) in combination with biodegradable conduits in peripheral nerve regeneration.
Materials & Methods: 20 male Wistar rats (8-12 weeks old) were divided in 4 groups (5 rats/group). Groups A and B were the control groups, whereas C and D the experimental groups. A complete transection of the sciatic nerve and a 10mm nerve defect was created in all rats. In Group A, 10mm of the sciatic nerve were removed and subsequently recoaptated in lieu of a reversed autograft. In the rest of the groups (B, C and D) the nerve defect was bridged with the use of a biodegradable nerve conduit. In the conduits of group B normal saline was applied, while the conduits of group C were enhanced with undifferentiated stem cells, and the conduits of group D with FK506. The cells were already harvested and cultured in a previous occasion. Peripheral nerve regeneration was evaluated in all rats 12 weeks later. Gait analysis was conducted in all rats and the sciatic functional index was calculated. Additionally, the repaired sciatic nerves were evaluated by electrophysiological studies and histology.
Results: The mean SFI in 12 weeks was impressively reduced in groups A (-63), C (-59) and D in comparison with group B (-74) However, statistical evaluation was not feasible due to the small sample size. Increased compound muscle action potential, and reduced nerve conduction latency of the repaired sciatic nerves were documented in the electrophysiological studies in all groups. Nevertheless, these results could not be quantified. Histology revealed more nerve axons and thicker myelin sheath formation in the site of the nerve gap and distally in groups C and D.
Conclusions: Successful peripheral nerve regeneration can be accomplished after a 10mm nerve gap. Autografts provide superior regeneration; however, nerve conduits may provide a very good outcome, too. Superior peripheral nerve regeneration was observed when undifferentiated stem cells or FK506 were applied. More data and statistical evidence is expected after conduction of the study in a bigger sample size.
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