Functional Results of Peripheral Nerve Repair with Epineural Tube Supported with Bone Marrow Stromal Cells are Comparable to Autograft Repair and Superior to Vein Tubulization Technique
Grzegorz Brzezicki, MD, Tim Nijhuis, MD, William Duggan, MD, Aleksandra Klimczak, PhD, James Gatherwright, Maria Siemionow, MD, PhD, DSc.
Cleveland Clinic, Cleveland, OH, USA.
PURPOSE:
Peripheral nerve defects repair remains a major challenge for surgeons. Biological conduit repair, supported with BMSC, can provide alternative method to autograft repair. This study compares the efficacy of peripheral nerve repair with autograft, isogenic epineural and vein conduit.
METHODS:
30 sciatic nerve gap (20mm) repairs were performed in 5 groups. In Group 1 nerve gap was repaired with autograft, in Group 2 - isogenic epineural tube filled with saline, Group 3 - isogenic epineural tube supported with 3.5-4 x106 of PKH stained BMSC. In Groups 4 and 5 the gap was bridged with isogenic vein filled with saline or isogenic PKH stained BMSC respectively. Animals were evaluated clinically for nerve regeneration with pinprick (PP) and toe-spread test (TS) at 6 and 12 weeks post repair. Assessment at 12 wks also included: Somatosensory Evoked Potentials (SSEP), Gastrocnemius Muscle Index (GMI), immunostaining for nerve growth factor (NGF) and Laminin B2.
RESULTS:
6 weeks after repair, Group 2 and 3 had significantly higher TS scores compared to Group 4 (1,33; 1,5 vs 0,63) and were comparable with autograft group (1,0). However, Group 5 had significantly better PP scores than Group 2 and 3 (3,0 vs 2,5; 2,5) at 6 weeks, while at 12 weeks there were no significant differences between all groups. GMI was comparable in Group 1, 2 and 3 (0,43; 0,39; 0,37) and significantly lower in Group 4 and 5 (0,17; 0,2). There were no significant differences in SSEP P1 and N2 latencies between groups. Group 4 and 5 had significantly lower amplitudes compared to Group 1 (31; 32 vs 70%). Immunostaining revealed high Laminin B2 and NGF expression in Group 1, lower in Group 2 and 3 and the lowest in vein groups. NGF expression in Group 3 and 5 correlated with double positive PKH/NGF BMSC.
CONCLUSION:
We proved that epineural tube is a viable conduit, supporting nerve regeneration over 20 mm defect. Obtained functional results are comparable to the autograft repair and significantly better than those in vein repair. Presence of BMSC was confirmed inside the epineural and vein conduit at 3 months post surgery and correlated with expression of NGF.