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一种用于原代肝细胞培养的混合基质,可在低血清依赖性条件下增强肝脏功能。

A hybrid substratum for primary hepatocyte culture that enhances hepatic functionality with low serum dependency.

作者信息

Meng Qingyuan, Tao Chunsheng, Qiu Zhiye, Akaike Toshihiro, Cui Fuzhai, Wang Xiumei

机构信息

School of Materials Science and Engineering, Tsinghua University, Beijing, People's Republic of China ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China ; Biomaterials Center for Regenerative Medical Engineering, Ibaraki, Japan.

School of Materials Science and Engineering, Tsinghua University, Beijing, People's Republic of China ; The 401 Hospital of Chinese People's Liberation Army, Qingdao, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Mar 23;10:2313-23. doi: 10.2147/IJN.S75011. eCollection 2015.

Abstract

Cell culture systems have proven to be crucial for the in vitro maintenance of primary hepatocytes and the preservation of hepatic functional expression at a high level. A poly-(N-p-vinylbenzyl-4-O-β-D-galactopyranosyl-D-gluconamide) matrix can recognize cells and promote liver function in a spheroid structure because of a specific galactose-asialoglycoprotein receptor interaction. Meanwhile, a fusion protein, E-cadherin-Fc, when incubated with various cells, has shown an enhancing effect on cellular viability and metabolism. Therefore, a hybrid substratum was developed for biomedical applications by using both of these materials to combine their advantages for primary hepatocyte cultures. The isolated cells showed a monolayer aggregate morphology on the coimmobilized surface and displayed higher functional expression than cells on traditional matrices. Furthermore, the hybrid system, in which the highest levels of cell adhesion and hepatocellular metabolism were achieved with the addition of 1% fetal bovine serum, showed a lower serum dependency than the collagen/gelatin-coated surface. Accordingly, this substrate may attenuate the negative effects of serum and further contribute to establishing a defined culture system for primary hepatocytes.

摘要

细胞培养系统已被证明对于原代肝细胞的体外维持以及高水平肝功能表达的保存至关重要。聚(N - 对乙烯基苄基 - 4 - O - β - D - 吡喃半乳糖基 - D - 葡糖酰胺)基质由于特定的半乳糖 - 去唾液酸糖蛋白受体相互作用,能够识别细胞并以球体结构促进肝功能。同时,融合蛋白E - 钙黏蛋白 - Fc与各种细胞孵育时,已显示出对细胞活力和代谢的增强作用。因此,通过使用这两种材料结合它们在原代肝细胞培养中的优势,开发了一种用于生物医学应用的混合基质。分离的细胞在共固定表面呈现单层聚集形态,并且比传统基质上的细胞表现出更高的功能表达。此外,在添加1%胎牛血清时实现最高水平细胞黏附和肝细胞代谢的混合系统,比胶原/明胶包被表面显示出更低的血清依赖性。因此,这种基质可能减轻血清的负面影响,并进一步有助于建立用于原代肝细胞的限定培养系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01eb/4376262/f21b1a4eea1d/ijn-10-2313Fig1.jpg

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