Artificial nerve graft using adipose-derived regenerative cells promotes peripheral nerve regeneration

近年は幹細胞を用いた人工神経の研究が進んでいる．今回我々は臨床応用を念頭に置き，脂肪組織由来再生細胞 (adipose derived regenerative cells, ADRCs) を封入した人工神経を作成し，その短期成績について検討した．体重2.5 ～3.0kgの日本白色家兎の右側の坐骨神経を切離し，15mmの欠損部を内径3.5mmの管腔物で架橋した．実験群は管腔物，封入物により分類し，I群はシリコンチューブと生理食塩水，II群は人工神経と生理食塩水， III群は人工神経とADRCs，IV群は自家神経移植群とした．各群5羽の計20羽を作成し，肉眼的評価，病理学的評価および電気生理学的評価を行った．肉眼的評価では全例に組織の連続性を認めたが，I群と比較しII，III，IV群では管腔内に組織が充満していた．病理学的評価では，I群と比較しII，III，IV群において髄鞘化の始まった線維像が認められ，特にIV群において顕著であった．また有髄線維数はIV，III，II，I群の順で多くなっており，各群間に有意差を認めた．電気生理学的評価ではIII 群，IV群の成績が良好であったが，各群間には有意差を認めなかった．本研究の結果，ADRCsは神経再生を促進すると考えられ，今後さらに解析を進めることで臨床応用できる可能性があると考えられた．Recently, great progress has been made in the development of stem cell-containing artificial nerve grafts. The present study evaluated the feasibility of an artificial nerve graft containing adipose-derived regenerative cells (ADRCs) for clinical application and examined its short-term results in Japanese white rabbit. In this model, the right sciatic nerve was excised, and a 15 mm gap was bridged by lumen material (3.5 mm). The animals were divided into four groups according to the type of lumen and enclosed material: group I, silicon tube and saline; group II, artificial nerve graft and saline; group III, artificial ner ve graft and ADRCs; and group IV, autologous ner ve graft (n = 5). The macroscopic, pathological, and electrophysiological findings were subsequently evaluated at 4 weeks and 8 weeks postoperatively. The macroscopic findings revealed that the lumina of group I contained less material than those of groups II, III, and IV. The pathological findings indicated a higher prevalence of myelinated fibers in groups II, III, and IV than in group I, which was the most prominent in group IV. The prevalence of myelinated fibers increased in the following order: groups I, II, III, and IV; significant differences were observed among the groups. The electrophysiological findings showed good results in groups III and IV; however, there was no significant difference between groups. The results revealed nerve regeneration by ADRCs. Therefore, the artificial nerve graft containing ADRCs is effective in promoting nerve regeneration, but not as effective as an autologous nerve graft