Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA.
Tissue Eng Part C Methods. 2010 Oct;16(5):1157-65. doi: 10.1089/ten.TEC.2009.0760.
The increased incidence of both type 2 diabetes mellitus and obesity has prompted the need to develop physiologically relevant adipose tissue models for controlled study of both normal and diseased adipose functions. Insulin resistance, characteristic of both type 2 diabetes mellitus and obesity, is often preceded by hyperinsulinemia. We propose here a three-dimensional (3D) co-culture adipose tissue model to study the effects of high insulin exposure, which enabled the study of physiological cell responses to hyperinsulinemic conditions. Two-dimensional adipocyte studies were initially conducted to establish a baseline control in which insulin levels were established. Adipocytes and endothelial cells were subsequently co-cultured on 3D porous silk fibroin scaffolds in normal or high insulin concentrations, and their physiological responses were assessed with respect to lipogenesis and lipolysis. High insulin levels stimulated both an increase in triglyceride accumulation and a decrease in lipolysis levels compared to that of normal insulin conditions. In contrast, adipocyte monocultures did not exhibit any differences between insulin levels. The ability of this 3D system to elicit physiological responses to hyperinsulinemia in co-culture serves as a significant step forward in adipose tissue engineering. The development of physiologically relevant 3D in vitro adipose tissue models presents promise for the study of disease mechanisms as well as in assessing therapeutic treatments.
2 型糖尿病和肥胖症发病率的增加促使人们需要开发与生理相关的脂肪组织模型，以便对正常和病态脂肪功能进行受控研究。胰岛素抵抗是 2 型糖尿病和肥胖症的特征，通常先于高胰岛素血症。在这里，我们提出了一种三维（3D）共培养脂肪组织模型，以研究高胰岛素暴露的影响，这使得研究生理细胞对高胰岛素血症条件的反应成为可能。首先进行了二维脂肪细胞研究，以建立一个基线对照，确定胰岛素水平。随后，将脂肪细胞和内皮细胞共培养在 3D 多孔丝素纤维支架上，分别在正常或高胰岛素浓度下，评估它们在脂肪生成和脂肪分解方面的生理反应。与正常胰岛素条件相比，高胰岛素水平刺激甘油三酯积累增加和脂肪分解水平降低。相比之下，脂肪细胞的单培养在胰岛素水平之间没有表现出任何差异。该 3D 系统在共培养中对高胰岛素血症产生生理反应的能力是脂肪组织工程向前迈出的重要一步。开发与生理相关的 3D 体外脂肪组织模型有望用于研究疾病机制以及评估治疗方法。
