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A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days

机译:标准化的基于胶原蛋白的支架可改善人肝细胞的运输,并允许在10天内进行代谢研究

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Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days.
机译:由于明显的物种差异,在动物研究中通常无法检测到新药的肝毒性。或者,可以使用人肝细胞,但是有一些限制。这些细胞并非总是能按需提供或有足够数量,到目前为止,只有很少的成功可以使新鲜分离的肝细胞得以运输,而不会长时间丧失其功能或对其进行长时间的培养。由于公认3D肝细胞的培养与功能的改善有关,因此我们在这里测试了Matricel的Optimaix-3D支架用于肝细胞的运输和培养。表征支架后,我们将细胞运送到支架上和/或培养10天以上。通过评估肝细胞功能(如尿素生成,白蛋白合成和CYP活性),我们显示了支架上细胞的代谢活性在培养时间内几乎保持恒定,而2D培养中代谢活性显着下降。此外,我们证明运输过程中损失的细胞明显减少。总之,基于胶原的支架允许肝细胞的运输和培养在10天内没有功能丧失。

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