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A medium hyperglycosylated podocalyxin enables noninvasive and quantitative detection of tumorigenic human pluripotent stem cells

机译:中等的高糖基化足蛋白可实现无创和定量检测致瘤性人多能干细胞

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摘要

While human pluripotent stem cells are attractive sources for cell-replacement therapies, a major concern remains regarding their tumorigenic potential. Thus, safety assessment of human pluripotent stem cell-based products in terms of tumorigenicity is critical. Previously we have identified a pluripotent stem cell-specific lectin probe rBC2LCN recognizing hyperglycosylated podocalyxin as a cell surface ligand. Here we demonstrate that hyperglycosylated podocalyxin is secreted from human pluripotent stem cells into cell culture supernatants. We establish a sandwich assay system, named the GlycoStem test, targeting the soluble hyperglycosylated podocalyxin using rBC2LCN. The GlycoStem test is sufficiently sensitive and quantitative to detect residual human pluripotent stem cells. This work provides a proof of concept for the noninvasive and quantitative detection of tumorigenic human pluripotent stem cells using cell culture supernatants. The developed method should increase the safety of human pluripotent stem cell-based cell therapies.
机译:尽管人类多能干细胞是细胞替代疗法的诱人来源,但人们对其致癌潜力的关注仍是主要问题。因此,就致癌性而言,对人类多能干细胞基产品的安全性评估至关重要。以前,我们已经确定了一种多能干细胞特异性凝集素探针rBC2LCN,它识别糖基化高糖化的podocalyxin为细胞表面配体。在这里,我们证明高糖基化的podoocalyxin是从人多能干细胞分泌到细胞培养上清液中的。我们建立了一个三明治检测系统,名为GlycoStem测试,使用rBC2LCN靶向可溶的高糖基化鬼臼毒素。 GlycoStem测试具有足够的灵敏度和定量能力,可以检测残留的人多能干细胞。这项工作为使用细胞培养上清液无创和定量检测致瘤性人多能干细胞提供了概念验证。发达的方法应提高基于人类多能干细胞的细胞疗法的安全性。

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