Adipose-Derived Stem Cell Sheets Prepared with Ascorbate 2-Phosphate Enhance Nerve Regeneration in Rat Sciatic Nerve Autografts

Background: Autologous nerve grafts remain the gold standard for peripheral nerve repair but have limited regenerative potential. Adipose-derived stem cells (ADSCs) have been investigated for their potential in nerve regeneration, and ascorbate 2-phosphate (A2P) enables the formation of ADSC sheets. This study examined whether ADSC sheets applied around autologous nerve grafts enhance functional and histological recovery in a rat sciatic nerve model. Methods: A 15 mm sciatic nerve segment was excised, inverted, and sutured for autologous grafting in rats. Three groups were compared: phosphate-buffered saline (PBS, control), ADSC suspension, and ADSC sheets. Functional recovery was assessed at 12 weeks (n = 10 per group) using the sciatic functional index (SFI), nerve conduction studies (latency, amplitude), and tibialis anterior muscle wet weight. Histological analyses, including toluidine blue staining, evaluated axonal changes at 1, 2, 4, 8, and 12 weeks (n = 3 per group per time point). DiI-labeled ADSCs were tracked at 1 week to assess cell retention (n = 3 per group). Results: At 12 weeks, the ADSC sheet group showed significantly improved SFI and muscle wet weight compared to controls and ADSC suspension groups. Nerve conduction studies revealed shorter distal latency in the ADSC sheet group versus controls, with no significant differences in the suspension group. While histological analysis did not demonstrate statistically significant differences among the groups, qualitative observations suggested that the ADSC sheet group tended to exhibit a greater number of myelinated axons at 12 weeks and fewer degenerative changes at earlier time points (1 and 2 weeks). DiI-labeled ADSCs were more frequently observed around the graft in the sheet group compared to the suspension group. Conclusion: Application of ADSC sheets to autologous nerve grafts may promote functional recovery. Forming ADSC sheets with A2P may represent a favorable approach for improving outcomes in peripheral nerve repair.

Publikationsverlauf

Eingereicht: 22. März 2025

Angenommen nach Revision: 27. Juli 2025

Accepted Manuscript online:
31. Juli 2025