Biomedical Engineering, Tufts University, Medford, MA, USA.
J Tissue Eng Regen Med. 2018 Mar;12(3):840-847. doi: 10.1002/term.2572. Epub 2017 Nov 10.
Obesity is a risk factor for a myriad of diseases including diabetes, cardiovascular dysfunction, cirrhosis, and cancer, and there is a need for new systems to study how excess adipose tissue relates to the onset of disease processes. This study provides proof-of-concept patient-specific tissue models of human white adipose tissue to accommodate the variability in human samples. Our 3D tissue engineering approach established lipolytic responses and changes in insulin-stimulated glucose uptake from small volumes of human lipoaspirate, making this methodology useful for patient specific sample source assessments of treatment strategies, drug responses, disease mechanisms, and other responses that vary between patients. Mature unilocular cells were maintained ex vivo in silk porous scaffolds for up to a month of culture and imaged non-invasively with coherent anti-Stokes Raman scattering. Interestingly, differences in responsiveness between tissues were observed in terms of magnitude of lipolysis, ability to suppress lipolysis, differences in glucose uptake, and lipid droplet size. Body mass index was not a factor in determining tissue responsiveness; rather, it is speculated that other unknown variables in the backgrounds of different patients (ethnicity, athleticism, disease history, lifestyle choices, etc.) likely had a more significant effect on the observed differences. This study reinforces the need to account for the variability in backgrounds and genetics within the human population to determine adipose tissue responsiveness. In the future, this tissue system could be used to inform individualized care strategies-enhancing therapeutic precision, improving patient outcomes, and reducing clinical costs.
肥胖是多种疾病的风险因素，包括糖尿病、心血管功能障碍、肝硬化和癌症，因此需要新的系统来研究过多的脂肪组织与疾病发生过程的关系。本研究提供了概念验证的患者特异性人白色脂肪组织组织模型，以适应人类样本的可变性。我们的 3D 组织工程方法从少量人脂肪抽吸物中建立了脂肪分解反应和胰岛素刺激的葡萄糖摄取变化，使得这种方法对于患者特定的样本来源评估治疗策略、药物反应、疾病机制和其他在患者之间变化的反应非常有用。成熟的单房细胞在丝素多孔支架中体外培养长达一个月，并通过相干反斯托克斯拉曼散射进行非侵入性成像。有趣的是，组织之间的反应性差异表现在脂肪分解的幅度、抑制脂肪分解的能力、葡萄糖摄取的差异和脂滴大小上。体重指数不是决定组织反应性的因素；而是推测不同患者背景中的其他未知变量（种族、运动能力、病史、生活方式选择等）可能对观察到的差异有更显著的影响。这项研究强调了需要考虑人类群体中背景和遗传的可变性，以确定脂肪组织的反应性。在未来，这种组织系统可以用于为个体化护理策略提供信息——提高治疗精度，改善患者预后，降低临床成本。
