Sustainable Three-Dimensional Tissue Model of Human Adipose Tissue

Sustainable Three-Dimensional Tissue Model of Human Adipose Tissue
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DOI:
10.1089/ten.tec.2012.0620
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发表时间:
2013-10-01
影响因子:
3
通讯作者:
Kaplan, David L.
Kaplan, David L.
中科院分区:
医学4区
文献类型:
--
作者:
Bellas, Evangelia;Marra, Kacey G.;Kaplan, David L.

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对于理解组织发育、疾病进展、体外药物开发和软组织再生来说,需要生理上相关的可持续人类脂肪组织模型是至关重要的。据报道,从人类脂肪干细胞分化而来的脂肪细胞与内皮细胞在多孔丝蛋白基质上共培养至少6个月,同时保持脂肪样结果。对培养物的结构和形态(油红O含量和CD31表达)、代谢功能(瘦素、甘油产生、GLUT4和PPARγ基因表达)和细胞复制(DNA含量)进行评估。在静态培养中,共培养物在延长的时间内保持大小和形状,而在转瓶培养中,共培养物的直径增加了12.5%。与静态培养相比,旋转烧瓶培养产生了基于结构和功能的总体脂肪组织结果。这项工作建立了一个组织模型系统,由于这里展示的长期可持续功能,该系统可以应用于与人类脂肪组织相关的慢性代谢功能障碍系统的发展,如肥胖和糖尿病。
The need for physiologically relevant sustainable human adipose tissue models is crucial for understanding tissue development, disease progression, in vitro drug development and soft tissue regeneration. The coculture of adipocytes differentiated from human adipose-derived stem cells, with endothelial cells, on porous silk protein matrices for at least 6 months is reported, while maintaining adipose-like outcomes. Cultures were assessed for structure and morphology (Oil Red O content and CD31 expression), metabolic functions (leptin, glycerol production, gene expression for GLUT4, and PPAR gamma) and cell replication (DNA content). The cocultures maintained size and shape over this extended period in static cultures, while increasing in diameter by 12.5% in spinner flask culture. Spinner flask cultures yielded improved adipose tissue outcomes overall, based on structure and function, when compared to the static cultures. This work establishes a tissue model system that can be applied to the development of chronic metabolic dysfunction systems associated with human adipose tissue, such as obesity and diabetes, due to the long term sustainable functions demonstrated here.