Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.
Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.
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精氨酸-甘氨酸-天冬氨酸-聚乙二醇-聚酰胺胺树枝状聚合物缀合物可改善 3-D 球体培养中的肝细胞聚集和功能
DOI：
10.2147/ijn.s113407
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发表时间：
2016
影响因子：
8
通讯作者：
Tang N
中科院分区：
文献类型：
--
作者：
Chen Z;Lian F;Wang X;Chen Y;Tang N
聚酰胺-胺（PAMAM）树枝状大分子是近年来在细胞培养和药物释放方面得到广泛应用的一类高分子材料。然而，PAMAM不参与肝细胞球体培养或其生物活性的研究，特别是在解毒功能方面。在这里，我们构建了一个PAMAM-树枝状大分子共轭物装饰的整合素配体：甘氨酸-天冬氨酸（RGD）肽。我们的研究表明，RGD-聚乙二醇（PEG）-PAMAM共轭物可以促进单个漂浮的肝细胞聚集在一起，在一个球样生长与弱活性氧。此外，RGD-PEG-PAMAM缀合物可以激活肝细胞中的AKT-MAPK通路，以促进细胞增殖，改善基本功能和氨代谢。总之，我们的数据支持RGD-PEG-PAMAM缀合物处理的肝细胞球作为生物人工肝系统的肝细胞的潜在来源。
The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine–glycine–aspartic acid (RGD) peptide. Our studies demonstrate that RGD–polyethylene glycol (PEG)–PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT–MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.