Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Brain Res. 2009 Dec 15;1303:26-31. doi: 10.1016/j.brainres.2009.09.073. Epub 2009 Sep 24.
Previous studies from our laboratory reported that transplantation of a mixture of 50% p75+ olfactory ensheathing cells (OECs) and fibroblasts derived from the outer layers of the adult olfactory bulb into unilateral lesions of the rat corticospinal tract (CST) restore function in a directed fore-paw retrieval task and induce regeneration of severed CST axons across the lesion. For future clinical application it would be preferable to obtain reparative cells from an olfactory mucosal biopsy via intranasal endoscopy rather than requiring the more invasive intracranial approach to remove an olfactory bulb. With this purpose, we used our original CST lesion paradigm to examine whether mucosal OEC preparations can provide a similar repair to those from the bulb. We found that, as in the case of bulbar OEC preparations, the mucosal cells also restored directed fore-paw retrieval. Surprisingly, however, there was no evidence of any of the severed CST axons crossing the lesion site, suggesting that the recovery of function is due to some other reaction, such as sprouting of damaged or undamaged fibres. Compared with the previous findings with bulbar cells, the mucosal cell cultures contained only 5% of OECs and a conversely much larger proportion of fibroblasts. These cell preparations showed minimal migratory ability and failed to form complete bridges across the lesions.
先前我们实验室的研究报告指出,将 50%的 p75+嗅鞘细胞(OECs)和源自成年嗅球外层的成纤维细胞混合物移植到大鼠皮质脊髓束(CST)单侧损伤中,可恢复定向前爪取回任务的功能,并诱导损伤处切断的 CST 轴突再生。为了未来的临床应用,通过鼻内内窥镜从嗅黏膜活检中获得修复细胞,而不是采用更具侵入性的颅内方法来移除嗅球,可能会更好。为此,我们使用了我们原始的 CST 损伤范例,来检查黏膜 OEC 制剂是否可以提供类似于嗅球制剂的修复作用。我们发现,与嗅球 OEC 制剂的情况一样,黏膜细胞也可以恢复定向前爪取回。然而,令人惊讶的是,没有任何切断的 CST 轴突穿过损伤部位的证据,这表明功能的恢复是由于其他反应,如受损或未受损纤维的发芽。与先前关于嗅球细胞的发现相比,黏膜细胞培养物仅含有 5%的 OECs,而相反地,成纤维细胞的比例要大得多。这些细胞制剂表现出最小的迁移能力,并且无法在损伤处形成完整的桥接。