Aix Marseille Univ, CNRS, ISM, UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité des Systèmes Nerveux et Musculaire (PSNM), Parc Scientifique et Technologique de Luminy, Faculté des Sciences du Sport de Marseille, CEDEX 09, F-13288 Marseille, France.
Aix Marseille Univ, CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), CEDEX 15, F-13344 Marseille, France.
Int J Mol Sci. 2020 Apr 11;21(8):2670. doi: 10.3390/ijms21082670.
Over the recent years, several methods have been experienced to repair injured peripheral nerves. Among investigated strategies, the use of natural or synthetic conduits was validated for clinical application. In this study, we assessed the therapeutic potential of vein guides, transplanted immediately or two weeks after a peroneal nerve injury and filled with olfactory ecto-mesenchymal stem cells (OEMSC). Rats were randomly allocated to five groups. A3 mm peroneal nerve loss was bridged, acutely or chronically, with a 1 cm long femoral vein and with/without OEMSCs. These four groups were compared to unoperated rats (Control group). OEMSCs were purified from male olfactory mucosae and grafted into female hosts. Three months after surgery, nerve repair was analyzed by measuring locomotor function, mechanical muscle properties, muscle mass, axon number, and myelination. We observed that stem cells significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. OEMSCs remained in the nerve and did not migrate in other organs. These results open the way for a phase I/IIa clinical trial based on the autologous engraftment of OEMSCs in patients with a nerve injury, especially those with neglected wounds.
近年来,人们已经尝试了多种修复周围神经损伤的方法。在研究的策略中,天然或合成导管的使用已被验证可用于临床应用。在这项研究中,我们评估了静脉引导物的治疗潜力,这些静脉引导物在腓神经损伤后立即或两周后移植,并填充有嗅外胚层间充质干细胞(OEMSC)。大鼠被随机分配到五个组。通过使用 1 厘米长的股静脉桥接腓神经 3 毫米的缺失,急性或慢性地桥接,同时伴有/不伴有 OEMSC。这四个组与未手术的大鼠(对照组)进行了比较。OEMSC 是从雄性嗅黏膜中纯化出来的,并移植到雌性宿主中。手术后 3 个月,通过测量运动功能、肌肉力学特性、肌肉质量、轴突数量和髓鞘化来分析神经修复情况。我们观察到,干细胞显著地:(i)增加了运动功能的恢复,(ii)部分维持了靶肌肉的收缩表型,(iii)增加了生长轴突的数量。OEMSC 留在神经中,没有迁移到其他器官。这些结果为基于自体移植 OEMSC 治疗神经损伤患者的 I/IIa 期临床试验铺平了道路,特别是那些患有被忽视的伤口的患者。