Prolongation of liver-specific function for primary hepatocytes maintenance in 3D printed architectures.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2018-01-02 Epub Date: 2018-02-01 DOI:10.1080/15476278.2018.1423931
Yohan Kim, Kyojin Kang, Sangtae Yoon, Ji Sook Kim, Su A Park, Wan Doo Kim, Seung Bum Lee, Ki-Young Ryu, Jaemin Jeong, Dongho Choi
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引用次数: 27

Abstract

Isolated primary hepatocytes from the liver are very similar to in vivo native liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells (MSCs) as an attractive assistant cell source to extend lifespan can be used, it cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture leads to cell death because of hypoxic stress. Therefore, to overcome the drawback of 2D and 3D organoids, we try to use a 3D printing technique using alginate hydrogels with primary hepatocytes and MSCs. The viability of isolated hepatocytes was more than 90%, and the cells remained alive for 7 days without morphological changes in the 3D hepatic architecture with MSCs. Compared to a 2D system, the expression level of functional hepatic genes and proteins was higher for up to 7 days in the 3D hepatic architecture. These results suggest that both the 3D bio-printing technique and paracrine molecules secreted by MSCs supported long-term culture of hepatocytes without morphological changes. Thus, this technique allows for widespread expansion of cells while forming multicellular aggregates, may be applied to drug screening and could be an efficient method for developing an artificial liver.

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3D打印结构中原发性肝细胞维持的肝脏特异性功能延长。
从肝脏分离的原代肝细胞与体内天然肝细胞非常相似,但它们在二维培养中存在寿命有限的缺点。虽然夹层培养和具有间充质干细胞(MSCs)的三维类器官可以作为延长寿命的有吸引力的辅助细胞来源,但它不能完全复制体内结构。此外,长期3D培养会导致细胞因缺氧应激而死亡。因此,为了克服2D和3D类器官的缺点,我们尝试使用海藻酸盐水凝胶与原代肝细胞和间充质干细胞进行3D打印技术。分离的肝细胞存活率超过90%,在MSCs的三维肝脏结构中,细胞存活7天,无形态学改变。与2D系统相比,在3D肝脏结构中,功能肝脏基因和蛋白质的表达水平最高可达7天。这些结果表明,3D生物打印技术和MSCs分泌的旁分泌分子都支持肝细胞长期培养而不发生形态学改变。因此,该技术允许细胞在形成多细胞聚集体的同时广泛扩增,可应用于药物筛选,并可能成为开发人工肝脏的有效方法。
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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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