title: Peripheral nerve repair of transplanted undifferentiated adipose tissue-derived stem cells in a biodegradable reinforced nerve conduit.
abstract: This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an improved approach to patient care.
authors.affiliation: Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Chiung-Chyi
authors.initials: CC
authors.lastname: Shen
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Yang
authors.forename: Bai-Shuan
authors.initials: BS
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005780:Gelatin / Q000494:pharmacology; D039823:Iridoids / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D039823:Iridoids; D005780:Gelatin; C007834:genipin; C018392:tricalcium phosphate