Xenogeneic acellular nerve grafts laden with Schwann cell-like cells repair monkey long-gap facial nerve defects

This study evaluated whether hair follicle epidermal neural crest stem cell-derived Schwann cell-like cells (HF-EPI-NCSC-SCLCs) could enhance the performance of cable-type porcine acellular nerve grafts (ANGs) in repairing long-gap whole facial nerve defects (WFNDs) in rhesus monkeys. Following chemical decellularization, porcine ANGs lacked S100B, α-Gal and swine leukocyte antigen expression, while laminin was well preserved. Cultured monkey HF-EPI-NCSC-SCLCs expressed Schwann cell markers (GFAP + /S100B +), exhibited low immunogenicity, and demonstrated vigorous growth in porcine ANGs in vitro. Twelve monkeys were randomly assigned to three equal groups: autologous sural nerve graft, ANG alone, and ANG + HF-EPI-NCSC-SCLCs. Each group received a graft to bridge a 35-mm-long WFND. At 8 months postoperatively, the ANG + HF-EPI-NCSC-SCLCs group showed significantly better facial symmetry, mimetic recovery, and recovery ratios of onset latency and amplitude than the ANG group. Severe synkinesis was frequent in the ANG group but only occasional in the other two groups. Nerve regeneration indices were also significantly improved with cell supplementation. No notable systemic or local immune responses differed among the three groups. These findings demonstrate that HF-EPI-NCSC-SCLCs effectively boost the regenerative capacity of cable-type xenogeneic ANGs for repairing long-gap WFNDs in non-human primates, supporting their translational potential for facial nerve reconstruction.