Department of Cell Biology, Medical School, University of Tampere, Tampere, Finland.
Tissue Eng Part A. 2012 Jan;18(1-2):17-25. doi: 10.1089/ten.TEA.2010.0712. Epub 2011 Oct 4.
The induction of adequate vascularization, a major challenge in tissue engineering, has been tried with numerous methods but with unsatisfactory results. Adipose tissue, an active endocrine organ with dense vasculature, secretes a wide number of angiogenic and adipogenic factors and seems an attractive source for these bioactive factors. We produced a novel cell-free extract from mature human adipose tissue (adipose tissue extract [ATE]) and analyzed the ability of this extract to induce angiogenesis and adipogenesis in vitro and studied the cytokine and growth factor composition of ATE with ELISA and cytokine array. We demonstrate that ATE, when added as cell culture supplement, effectively induced triglyceride accumulation in human adipose stem cells at concentrations from 200 μg/mL upward in less than a week and caused elevated levels of adipocyte differentiation markers (proliferator-activated receptor gamma and acyl-CoA-binding protein) when treated with at least 350 μg/mL of ATE. ATE induced angiogenesis from 450 μg/mL upward after a week in vitro. ATE contained numerous angiogenic and adipogenic factors, for example, vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, adiponectin, angiogenin, leptin, and insulin-like growth factor-I, as well as lower levels of a wide variety of other cytokines. We here present a novel cell-free angiogenesis- and adipogenesis-inducing agent that is cell-free and easy to produce, and its effect is dose dependent and its composition can be easily modified. Therefore, ATE is a promising novel agent to be used for angiogenesis induction to overcome the challenge of vascularization and for adipogenesis induction in a wide variety of tissue engineering applications in vitro and in vivo. ATE is also efficient for reproduction and modeling of natural adipogenesis in vitro for, for example, obesity and diabetes studies.
诱导足够的血管生成是组织工程中的一个主要挑战，已经尝试了许多方法，但结果并不令人满意。脂肪组织是一种具有密集血管的活跃内分泌器官，分泌大量的血管生成和脂肪生成因子，似乎是这些生物活性因子的有吸引力的来源。我们从成熟的人类脂肪组织（脂肪组织提取物 [ATE]）中产生了一种新型的无细胞提取物，并分析了该提取物在体外诱导血管生成和脂肪生成的能力，并使用 ELISA 和细胞因子阵列研究了 ATE 的细胞因子和生长因子组成。我们证明，ATE 作为细胞培养补充剂添加时，在不到一周的时间内，以 200μg/mL 以上的浓度有效地诱导人脂肪干细胞中甘油三酯的积累，并且在用至少 350μg/mL 的 ATE 处理时引起脂肪细胞分化标志物（增殖激活受体γ和酰基辅酶 A 结合蛋白）的水平升高。ATE 在体外培养一周后，以 450μg/mL 以上的浓度诱导血管生成。ATE 包含许多血管生成和脂肪生成因子，例如血管内皮生长因子、碱性成纤维细胞生长因子、白细胞介素 6、脂联素、血管生成素、瘦素和胰岛素样生长因子-I，以及许多其他细胞因子的低水平。我们在此提出了一种新型的无细胞血管生成和脂肪生成诱导剂，它是无细胞的，易于生产，其作用是剂量依赖性的，其组成可以很容易地修改。因此，ATE 是一种很有前途的新型诱导血管生成的试剂，用于克服血管化的挑战，以及在体外和体内的各种组织工程应用中诱导脂肪生成。ATE 还可有效地用于体外天然脂肪生成的繁殖和建模，例如肥胖和糖尿病研究。
