Zhang Wenming, Fang Xinyu, Zhang Chaofan, Li Wen, Wong Wai Man, Xu Yejun, Wu Wutian, Lin Jianhua
Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Fuzhou 350005, Fujian, China.
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam 999077, Hong Kong SAR, China.
Eur J Neurosci. 2017 Mar;45(6):750-762. doi: 10.1111/ejn.13495. Epub 2017 Jan 23.
Peripheral nerve injury (PNI) usually results in poor functional recovery. Nerve repair is the common clinical treatment for PNI but is always obstructed by the chronic degeneration of the distal stump and muscle. Cell transplantation can alleviate the muscle atrophy after PNI, but the subsequent recovery of the locomotive function is seldom described. In this study, we combined cell transplantation and nerve repair to investigate whether the transplantation of embryonic spinal cord cells could benefit the delayed nerve repair. The experiment consisted of 3 stages: transection of the tibial nerve to induce 'pre-degeneration', a second surgery performed 2 weeks later for transplantation of E14 embryonic spinal cord cells or vehicle (culture medium) at the distal end of the injured nerve, and, 3 months later, the removal of the grafted cells and the cross-suturing of the residual distal end to the proximal end of a freshly cut ipsilateral common peroneal (CP) nerve. Cell survival and fate after the transplantation were investigated, and the functional recovery after the cross-suturing was compared between the groups. The grafted cells could survive and generate motor neurons, extending axons that were subsequently myelinated and forming synapses with the muscle. After the cross-suturing, the axonal regeneration from the proximal stump of the injured CP nerve and the functional recovery of the denervated gastrocnemius muscle were significantly promoted in the group receiving the cells. Our study presents a new perspective indicating that the transplantation of embryonic spinal cord neurons may be a valuable therapeutic strategy for PNI.
周围神经损伤(PNI)通常导致功能恢复不佳。神经修复是PNI常见的临床治疗方法,但总是受到远端残端和肌肉慢性退变的阻碍。细胞移植可以减轻PNI后的肌肉萎缩,但很少描述随后运动功能的恢复情况。在本研究中,我们将细胞移植与神经修复相结合,以研究胚胎脊髓细胞移植是否有利于延迟的神经修复。实验包括3个阶段:切断胫神经以诱导“预退变”,2周后进行第二次手术,在损伤神经的远端移植E14胚胎脊髓细胞或载体(培养基),3个月后,去除移植的细胞,并将残余远端与新切断的同侧腓总神经(CP)近端进行交叉缝合。研究了移植后细胞的存活和命运,并比较了各组交叉缝合后的功能恢复情况。移植的细胞能够存活并产生运动神经元,延伸的轴突随后被髓鞘化并与肌肉形成突触。交叉缝合后,接受细胞的组中,损伤CP神经近端残端的轴突再生和失神经支配的腓肠肌的功能恢复得到显著促进。我们的研究提出了一个新的观点,即胚胎脊髓神经元移植可能是PNI一种有价值的治疗策略。