Differentiated and undifferentiated adipose-derived stem cells improve function in rats with peripheral nerve gaps

Abstract

The effect of differentiated and undifferentiated adipose-derived stem cells on the repair of peripheral nerve gaps was studied. Adipose-derived stem cells were maintained in differentiation medium for 2 weeks. The expression of Schwann cell proteins S-100, nerve growth factor receptor (NGFR) p75 and integrin β4 was examined by immunofluorescence staining and real time-polymerase chain reaction (real time-PCR) at the end of the differentiation period. A 10-mm gap on the left sciatic nerves of 20 Fischer rats was created and bridged with silicone tube (group I), silicone tube filled with collagen gel (group II), nerve graft (group III), silicone tube filled with adipose-derived stem cells (group IV) and silicone tube filled with differentiated adipose-derived stem cells (group V). In vitro, the positivity of differentiated adipose-derived stem cells for S-100, NGFR p75 and integrin β4 by immunofluorescence staining was 31%, 27% and 12%, respectively. Fold changes by real time-PCR in comparison with undifferentiated cells were 48.4, 168.7 and 284.85, respectively. In vivo, a walking track analysis did not yield any statistically significant differences after 3 months postoperatively; however, after 6 months, group IV (sciatic function index (SFI) = -49.1 ± 13.1) and V (SFI = -52.6 ± 5.7) showed significant improvement compared to other groups (I: -73.3 ± 5.07, II: -79.6 ± 12.01, III: -74.8 ± 12.89) (p < 0.05). Nerve conduction velocity after 6 months was higher in groups IV (4.44 ± 0.3 mm ms(-1)), V (4.25 ± 0.3 mm ms(-1)) and III (4 ± 0.3 mm ms(-1)) than in groups I (2.5 ± 2.25 mm ms(-1)) and II (2.35 ± 1.58 mm ms(-1)) (p > 0.05). Myelin fibre density and myelinated fibre/unmyelinated fibre ratio were significantly higher in the midnerve and the distal nerve in groups IV and V (p < 0.05). These results reveal the therapeutic potential of adipose-derived stem cells in nerve reconstruction.