FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells
FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells
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DOI：
10.1002/glia.20025
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发表时间：
2004-08
期刊：
影响因子：
6.2
通讯作者：
E. Udina;F. Rodrı́guez;E. Verdú;M. Espejo;B. Gold;X. Navarro
中科院分区：
文献类型：
--
作者：
E. Udina;F. Rodrı́guez;E. Verdú;M. Espejo;B. Gold;X. Navarro
我们评估了在小鼠坐骨神经中使用接种同种异体雪旺细胞（SC）的胶原引导物进行6 mm间隙修复后，FK 506给药对再生的影响。从预变性的成人坐骨神经中分离SC，并使用确定的培养基在培养中扩增，然后接种在包埋在Matrigel中的胶原引导物中。通过非侵入性方法评估功能性神经再支配，以确定术后4个月后爪运动、感觉和自主神经功能的恢复情况。在研究结束时进行再生神经的组织学分析。使用简单的胶原蛋白导管进行小管化修复，免疫抑制剂剂量的FK 506（5 mg/kg/天）治疗可显著改善神经再支配的发生和程度。虽然与仅填充有Matrigel的胶原引导物相比，同种异体SC的引入没有改善再生，但是用FK 506治疗允许在所有小鼠中成功再生并且显著改善功能恢复水平。与未处理组相比，FK 506处理组动物中移植的预标记SC的存活率更高。在形态学上，使用FK 506给药动物的SC接种导向器获得了最佳神经再生（就神经口径和有髓轴突数量而言）。因此，FK 506应被视为各种类型输卵管化修复的辅助治疗。© 2004 Wiley利斯公司
We assessed the effects of FK506 administration on regeneration after a 6‐mm gap repair with a collagen guide seeded with allogeneic Schwann cells (SCs) in the mouse sciatic nerve. SCs were isolated from predegenerated adult sciatic nerves and expanded in culture using a defined medium, before being seeded in the collagen guide embedded in Matrigel. Functional reinnervation was evaluated by noninvasive methods to determine recovery of motor, sensory, and autonomic functions in the hindpaw over 4 months postoperation. Histological analysis of the regenerated nerves was performed at the end of the study. Using simple collagen guides for tubulization repair, treatment with an immunosuppressant dose of FK506 (5 mg/kg/day) resulted in significant improvement of the onset and the degree of reinnervation. While the introduction of allogeneic SCs did not improve regeneration versus a collagen guide filled only with Matrigel, treatment with FK506 allowed for successful regeneration in all the mice and for significant improvement in the levels of functional recovery. Compared with the untreated group, there was greater survival of transplanted pre‐labeled SCs in the FK506‐treated animals. Morphologically, the best nerve regeneration (in terms of nerve caliber and numbers of myelinated axons) was obtained with SC‐seeded guides from FK506‐treated animals. Thus, FK506 should be considered as adjunct therapy for various types of tubulization repair. © 2004 Wiley‐Liss, Inc.