A mechanistic understanding of adipose tissue differentiation is critical for the treatment and prevention of obesity and type 2 diabetes. Conventional in vitro models of adipogenesis are preadipocytes or freshly isolated adipocytes grown in two-dimensional (2D) cultures. Optimal results using in vitro tissue culture models can be expected only when adipocyte models closely resemble adipose tissue in vivo. Thus the design of an in vitro three-dimensional (3D) model which faithfully mimics the in vivo environment is needed to effectively study adipogenesis. Pluripotent embryonic stem (ES) cells are a self-renewing cell type that can readily be differentiated into adipocytes. In this study, a 3D culture system was developed to mimic the geometry of adipose tissue in vivo. Murine ES cells were seeded into electrospun polycaprolactone scaffolds and differentiated into adipocytes in situ by hormone induction as demonstrated using a battery of gene and protein expression markers along with the accumulation of neutral lipid droplets. Insulin-responsive Akt phosphorylation, and beta-adrenergic stimulation of cyclic AMP synthesis were demonstrated in ES cell-derived adipocytes. Morphologically, ES cell-derived adipocytes resembled native fat cells by scanning electron and phase contrast microscopy. This tissue engineered ES cell-matrix model has potential uses in drug screening and other therapeutic developments.

译文

:对脂肪组织分化的机械理解对于肥胖症和2型糖尿病的治疗和预防至关重要。脂肪形成的常规体外模型是在二维(2D)培养物中生长的前脂肪细胞或新鲜分离的脂肪细胞。仅当脂肪细胞模型与体内脂肪组织非常相似时,才能期望使用体外组织培养模型获得最佳结果。因此,需要忠实地模拟体内环境的体外三维(3D)模型的设计才能有效地研究脂肪形成。多能胚胎干(ES)细胞是一种自我更新的细胞类型,可以很容易地分化为脂肪细胞。在这项研究中,开发了一种3D培养系统来模拟体内脂肪组织的几何形状。将鼠ES细胞接种到电纺聚己内酯支架中,并通过激素诱导原位分化为脂肪细胞,如使用一系列基因和蛋白质表达标志物以及中性脂质滴的积累所证明的。在ES细胞衍生的脂肪细胞中证实了胰岛素反应性Akt磷酸化和β-肾上腺素能刺激环状AMP合成。形态上,通过扫描电子和相差显微镜,ES细胞来源的脂肪细胞类似于天然脂肪细胞。这种组织工程化的ES细胞基质模型在药物筛选和其他治疗发展中具有潜在用途。

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