Facilitatory effects of artificial nerve filled with adipose-derived stem cell sheets on peripheral nerve
Tadahiro Nakajima1, Kaoru Tada1, Mika Nakada1
1Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
Background:
We evaluated how artificial nerves filled with adipose-derived stem cell (ADSC) sheets could facilitate peripheral nerve regeneration.
Methods:
We prepared ADSC sheets following previously described protocols. We transected the sciatic nerve in 12-week-old Wistar rats, fixed the nerve ends to the artificial conduit, and prepared three groups: (1) conduits alone (control group); (2) conduits filled with ADSCs (ADSCs group), and (3) conduits filled with ADSC sheets (ADSC sheet group). We assessed the subjects 4 and 12 weeks post-transplantation (n = 24). We investigated βIII-tubulin and anti-S100 expression at 4 and 12 weeks post-transplantation, in longitudinal- and cross-sections of the central portion in the regenerated tissues. The vascular endothelial growth factor A (VEGFA) and neuregulin-1 expressions were analyzed using real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). We evaluated the tibialis anterior muscle wet weight (affected/healthy sides, %) and sciatic function index (SFI) 12 weeks post-transplantation.
Results:
The ADSC sheet group comprised more S100-positive cells than the other groups. The regenerated axon length in the ADSC sheet group was markedly the longest among the studied groups. The immunostaining revealed a positive area in the regenerated tissue center in all groups, tending to be the largest in the ADSC sheet group. The muscle wet weight indicated that the ADSC sheet group exhibited significantly higher weight than the control. The mean SFI showed that the ADSC sheet group exhibited significantly better results than the control. The VEGFA expression was higher both in the ADSC and the ADSC sheet group than in the control. The neuregulin-1 expression was higher both in the ADSC and the ADSC sheet group than in the control.
Conclusions:
The ADSC sheets could potentially support transplanting an adequate number of ADSCs at the target site. Compared with the conventional method of attaching ADSCs, the use of ADSC sheets promotes accelerated nerve regeneration.
