Repairing peripheral nerve defect with prevascularized artificial nerve

Abstract

Objective To evaluate the effectiveness of prevascularized acellular nerve graft combined with autologous differentiated adipose-derived stem cells on repairing nerve defect in rats.Methods Adiposederived stem cells (ADSCs) were isolated from rat inguinal fat pad.Vascular endothelial growth factor (VEGF) encapsulated nanoparticles were injected into the chemically decellularized nerve graft which in turn was buried into the incision for fat harvesting.The rat was kept for 2 weeks to allow prevascularization of the acellular nerve graft.The ADSCs were cultured under neurogeneic conditions for 2 weeks to differentiate into Schwann cells.A 15 mm sciatic nerve gap in rats was repaired by VEGF nanoparticle prevascularized acellular nerve graft injected with differentiated ADSCs (Group A),by non-VEGF nanoparticle prevascularized acellular nerve injected with differentiated ADSCs (Group B),by acellular nerve injected with differentiated ADSCs (Group C),by autologous nerve graft (Group D),and by VEGF nanoparticle prevascularized acellular nerve graft (Group E).On postoperative day 7 grafts from Groups A,B and C were harvested.Microvessel density (MVD) and graft cell apoptosis were examined.After 12 weeks,nerve conduction study,triceps surae muscle wet weight,and neuromorphometry analysis were carried out to evaluate the extent of nerve regeneration.Results Seven days postoperatively,graft cell apoptosis was most prominent in group C.Apoptosis in group A was less severe than Group B.MVD was highest in group A,followed by group B and then group C.Evaluations at 12 weeks postoperatively showed significantly higher nerve conduction velocity,larger action potential amplitude,higher triceps surae muscle weight recovery rate and larger myelinated nerve fiber count in Group A than in Group B,Group C and Group E (P ＜ 0.05).Conclusion There is a synergistic effect of acellular nerve and differentiated ADSCs in repairing nerve gap in rats.The prevascularized acellular nerve improves survival of transplanted cells,which is benefit for nerve regeneration. Key words: Nerve regeneration; Stem cells, mesenchymal; Prevascularization; Acellular nerve