Human embryonic and mesenchymal stem cell therapies may offer significant benefit to a large number of patients. Recently, however, human embryonic stem cell lines cultured on mouse feeder cells were reported to be contaminated by the xeno-carbohydrate N-glycolylneuraminic acid (Neu5Gc) and considered potentially unfit for human therapy. To determine the extent of the problem of Neu5Gc contamination for the development of stem cell therapies, we investigated whether it also occurs in cells cultured on human feeder cells and in mesenchymal stem cells, what are the sources of contamination, and whether the contamination is reversible. We found that N-glycolylneuraminic acid was present in embryonic stem cells cultured on human feeder cells, correlating with the presence of Neu5Gc in components of the commercial serum replacement culture medium. Similar contamination occurred in mesenchymal stem cells cultured in the presence of fetal bovine serum. The results suggest that the Neu5Gc is present in both glycoprotein and lipid-linked glycans, as detected by mass spectrometric analysis and monoclonal antibody staining, respectively. Significantly, the contamination was largely reversible in the progeny of both cell types, suggesting that decontaminated cells may be derived from existing stem cell lines. Although major complications have not been reported in the clinical trials with mesenchymal stem cells exposed to fetal bovine serum, the immunogenic contamination may potentially be reflected in the viability and efficacy of the transplanted cells and thus bias the published results. Definition of safe culture conditions for stem cells is essential for future development of cellular therapies.

译文

:人类胚胎和间充质干细胞疗法可能为许多患者带来重大益处。然而,最近,据报道,在小鼠饲养细胞上培养的人类胚胎干细胞系被异种碳水化合物N-甘氨酰神经氨酸(Neu5Gc)污染,被认为可能不适合人类治疗。为了确定Neu5Gc污染问题对干细胞疗法发展的影响程度,我们调查了它是否也在人类饲养细胞和间充质干细胞中培养的细胞中也发生了,污染的来源是什么,以及污染是否可逆。我们发现,在人类饲养细胞上培养的胚胎干细胞中存在N-羟乙酸神经氨酸,这与商业血清替代培养基成分中Neu5Gc的存在有关。在胎牛血清存在下培养的间充质干细胞中也发生了类似的污染。结果表明,分别通过质谱分析和单克隆抗体染色检测,Neu5Gc同时存在于糖蛋白和脂质连接的聚糖中。值得注意的是,两种细胞类型的后代中的污染在很大程度上都是可逆的,这表明去污染的细胞可能源自现有的干细胞系。尽管在间质干细胞暴露于胎牛血清的临床试验中尚未报告重大并发症,但免疫原性污染可能会反映在移植细胞的生存力和功效中,因此会影响已发表的结果。干细胞安全培养条件的定义对于细胞疗法的未来发展至关重要。

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