Oprych Karen, Cotfas Daniel, Choi David
Department of Brain, Repair and Rehabilitation, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Brain Struct Funct. 2017 May;222(4):1877-1895. doi: 10.1007/s00429-016-1313-y. Epub 2016 Oct 7.
The in situ immunocytochemical properties of olfactory ensheathing cells (OECs) have been well studied in several small to medium sized animal models including rats, mice, guinea pigs, cats and canines. However, we know very little about the antigenic characteristics of OECs in situ within the adult and developing human olfactory bulb and nerve roots. To address this gap in knowledge we undertook an immunocytochemical analysis of the 11-19 pcw human foetal olfactory system. Human foetal OECs in situ possessed important differences compared to rodents in the expression of key surface markers. P75 was not observed in OECs but was strongly expressed by human foetal Schwann cells and perineurial olfactory nerve fibroblasts surrounding OECs. We define OECs throughout the 11-19 pcw human olfactory system as S100/vimentin/SOX10+ with low expression of GFAP. Our results suggest that P75 is a robust marker that could be utilised with cell sorting techniques to generate enriched OEC cultures by first removing P75 expressing Schwann cells and fibroblasts, and subsequently to isolate OECs after P75 upregulation in vitro. O4 and PSA-NCAM were not found to be suitable surface antigens for OEC purification owing to their ambiguous and heterogeneous expression. Our results highlight the importance of corroborating cell markers when translating cell therapies from animal models to the clinic.
嗅觉鞘细胞(OECs)的原位免疫细胞化学特性已在包括大鼠、小鼠、豚鼠、猫和犬在内的几种中小型动物模型中得到了充分研究。然而,我们对成人和发育中的人类嗅球及神经根内原位OECs的抗原特性知之甚少。为了填补这一知识空白,我们对11-19孕周的人类胎儿嗅觉系统进行了免疫细胞化学分析。与啮齿动物相比,原位的人类胎儿OECs在关键表面标志物的表达上存在重要差异。在OECs中未观察到P75,但在人类胎儿雪旺细胞和围绕OECs的神经束膜嗅神经成纤维细胞中强烈表达。我们将11-19孕周的人类嗅觉系统中的OECs定义为S100/波形蛋白/SOX10阳性且GFAP表达较低。我们的结果表明,P75是一种可靠的标志物,可与细胞分选技术一起使用,通过首先去除表达P75的雪旺细胞和成纤维细胞,随后在体外上调P75后分离OECs,来生成富集的OECs培养物。由于O4和PSA-NCAM的表达模糊且不均一,它们不被认为是适合用于纯化OECs的表面抗原。我们的结果强调了在将细胞疗法从动物模型转化到临床时,确证细胞标志物的重要性。