Yang Feipeng, Carmona Alanis, Stojkova Katerina, Garcia Huitron Eric Ivan, Goddi Anna, Bhushan Abhinav, Cohen Ronald N, Brey Eric M
Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, 60616, USA.
Lab Chip. 2021 Jan 21;21(2):435-446. doi: 10.1039/d0lc00981d. Epub 2020 Dec 22.
An accurate in vitro model of human adipose tissue could assist in the study of adipocyte function and allow for better tools for screening new therapeutic compounds. Cell culture models on two-dimensional surfaces fall short of mimicking the three-dimensional in vivo adipose environment, while three-dimensional culture models are often unable to support long-term cell culture due, in part, to insufficient mass transport. Microfluidic systems have been explored for adipose tissue models. However, current systems have primarily focused on 2D cultured adipocytes. In this work, a 3D human adipose microtissue was engineered within a microfluidic system. Human adipose-derived stem cells (ADSCs) were used as the cell source for generating differentiated adipocytes. The ADSCs differentiated within the microfluidic system formed a dense lipid-loaded mass with the expression of adipose tissue genetic markers. Engineered adipose tissue showed a decreased adiponectin secretion and increased free fatty acid secretion with increasing shear stress. Adipogenesis markers were downregulated with increasing shear stress. Overall, this microfluidic system enables the on-chip differentiation and development of a functional 3D human adipose microtissue supported by the interstitial flow. This system could potentially serve as a platform for in vitro drug testing for adipose tissue-related diseases.
精确的人体脂肪组织体外模型有助于研究脂肪细胞功能，并为筛选新的治疗化合物提供更好的工具。二维表面上的细胞培养模型无法模拟三维体内脂肪环境，而三维培养模型往往因传质不足而无法支持长期细胞培养。微流控系统已被用于脂肪组织模型的研究。然而，目前的系统主要集中在二维培养的脂肪细胞上。在这项工作中，在微流控系统中构建了三维人体脂肪微组织。人脂肪来源干细胞（ADSCs）被用作生成分化脂肪细胞的细胞来源。在微流控系统中分化的ADSCs形成了一个富含脂质的致密团块，并表达脂肪组织遗传标记。随着剪切应力的增加，工程化脂肪组织的脂联素分泌减少，游离脂肪酸分泌增加。脂肪生成标记物随着剪切应力的增加而下调。总体而言，该微流控系统能够在芯片上实现由间质流支持的功能性三维人体脂肪微组织的分化和发育。该系统有可能作为脂肪组织相关疾病体外药物测试的平台。
