Guerout Nicolas, Paviot Alexandre, Bon-Mardion Nicolas, Honoré Axel, Obongo Rais, Duclos Célia, Marie Jean-Paul
UPRES EA3830, Institute for Research and Innovation in Biomedicine, University of Rouen; Neuroscience, Karolinska Institutet;
UPRES EA3830, Institute for Research and Innovation in Biomedicine, University of Rouen; Otorhinolaryngology, Head and Neck Surgery Department, Rouen University Hospital.
J Vis Exp. 2014 Feb 23(84):e50590. doi: 10.3791/50590.
Olfactory ensheathing cells (OECs) are neural crest cells which allow growth and regrowth of the primary olfactory neurons. Indeed, the primary olfactory system is characterized by its ability to give rise to new neurons even in adult animals. This particular ability is partly due to the presence of OECs which create a favorable microenvironment for neurogenesis. This property of OECs has been used for cellular transplantation such as in spinal cord injury models. Although the peripheral nervous system has a greater capacity to regenerate after nerve injury than the central nervous system, complete sections induce misrouting during axonal regrowth in particular after facial of laryngeal nerve transection. Specifically, full sectioning of the recurrent laryngeal nerve (RLN) induces aberrant axonal regrowth resulting in synkinesis of the vocal cords. In this specific model, we showed that OECs transplantation efficiently increases axonal regrowth. OECs are constituted of several subpopulations present in both the olfactory mucosa (OM-OECs) and the olfactory bulbs (OB-OECs). We present here a model of cellular transplantation based on the use of these different subpopulations of OECs in a RLN injury model. Using this paradigm, primary cultures of OB-OECs and OM-OECs were transplanted in Matrigel after section and anastomosis of the RLN. Two months after surgery, we evaluated transplanted animals by complementary analyses based on videolaryngoscopy, electromyography (EMG), and histological studies. First, videolaryngoscopy allowed us to evaluate laryngeal functions, in particular muscular cocontractions phenomena. Then, EMG analyses demonstrated richness and synchronization of muscular activities. Finally, histological studies based on toluidine blue staining allowed the quantification of the number and profile of myelinated fibers. All together, we describe here how to isolate, culture, identify and transplant OECs from OM and OB after RLN section-anastomosis and how to evaluate and analyze the efficiency of these transplanted cells on axonal regrowth and laryngeal functions.
嗅鞘细胞(OECs)是神经嵴细胞,可促进初级嗅觉神经元的生长和再生。事实上,即使在成年动物中,初级嗅觉系统的特征也是能够产生新的神经元。这种特殊能力部分归因于嗅鞘细胞的存在,它们为神经发生创造了有利的微环境。嗅鞘细胞的这一特性已被用于细胞移植,如在脊髓损伤模型中。虽然周围神经系统在神经损伤后比中枢神经系统具有更强的再生能力,但完全横断会在轴突再生过程中导致错误布线,尤其是在喉返神经切断后。具体而言,喉返神经(RLN)的完全横断会诱导异常的轴突再生,导致声带协同运动。在这个特定模型中,我们表明嗅鞘细胞移植能有效促进轴突再生。嗅鞘细胞由存在于嗅黏膜(OM - OECs)和嗅球(OB - OECs)中的几个亚群组成。我们在此展示了一种基于在RLN损伤模型中使用这些不同亚群嗅鞘细胞的细胞移植模型。使用这种范式,在RLN切断和吻合后,将OB - OECs和OM - OECs的原代培养物移植到基质胶中。手术后两个月,我们通过基于视频喉镜检查、肌电图(EMG)和组织学研究的补充分析对移植动物进行评估。首先,视频喉镜检查使我们能够评估喉部功能,特别是肌肉共同收缩现象。然后,EMG分析证明了肌肉活动的丰富性和同步性。最后,基于甲苯胺蓝染色的组织学研究能够对有髓纤维的数量和形态进行量化。总之,我们在此描述了如何在RLN切断 - 吻合后从OM和OB中分离、培养、鉴定和移植嗅鞘细胞,以及如何评估和分析这些移植细胞对轴突再生和喉部功能的作用效率。