Constructing three-dimensional (3D) tissues is an important process to improve cellular functions in tissue engineering. When transplanting artificially constructed tissues, a poor vascular network restricts oxygen and nutrient supplies to the tissue cells, which leads to cell death and reduced rates of tissue engraftment. Therefore, it is necessary to develop a system that builds a vascular network within 3D tissues. Here, we developed a hypoxia-responsive gene expression system for production of an angiogenic factor, vascular endothelial growth factor (VEGF), to improve hypoxia and nutrition deficiencies inside artificial 3D tissues. We demonstrated that cells into which the hypoxia-responsive VEGF gene expression system had been introduced autonomously controlled VEGF expression in a hypoxic stress-dependent manner. Next, we confirmed that VEGF expression within a 3D cell sheet was induced in response to a hypoxic environment in vitro. The genetically modified cell sheet was subcutaneously transplanted into mice to evaluate the feasibility of the hypoxia-responsive VEGF gene expression system in vivo. The results suggest that the hypoxia-responsive VEGF gene expression system is promising to prepare artificial 3D tissues in regenerative medicine.

构建三维 (3D) 组织是改善组织工程中细胞功能的重要过程。在移植人工构建的组织时，较差的血管网络会限制组织细胞的氧气和营养供应，从而导致细胞死亡和组织植入率降低。因此，有必要开发一种在 3D 组织内构建血管网络的系统。在这里，我们开发了一种缺氧响应基因表达系统，用于生产血管生成因子、血管内皮生长因子 (VEGF)，以改善人工 3D 组织内的缺氧和营养缺乏。我们证明了已引入缺氧响应 VEGF 基因表达系统的细胞以缺氧应激依赖性方式自主控制 VEGF 表达。下一个，体外。将转基因细胞片皮下移植到小鼠体内，以评估缺氧反应性VEGF基因表达系统在体内的可行性。结果表明，缺氧响应 VEGF 基因表达系统有望在再生医学中制备人工 3D 组织。