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Senescent Cells with Augmented Cytokine Production for Microvascular Bioengineering and Tissue Repairs

机译:用于微血管生物工程和组织修复的具有增强细胞因子产生的衰老细胞

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Abstract Controlled delivery of cytokines and growth factors has been an area of intense research interest for molecular and cellular bioengineering, immunotherapy, and regenerative medicine. This study shows that primary human lung fibroblasts chemically induced to senescence (cell cycle arrest) can act as a living source to transiently produce factors essential for promoting vasculogenesis or angiogenesis, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and interleukin 8 (IL‐8). Coculture of senescent fibroblasts with human umbilical vein endothelial cells in a fibrin gel demonstrate accelerated formation and maturation of microvessel networks in as early as three days. Unlike the usage of nonsenescent fibroblasts as the angiogenesis‐promoting cells, this approach eliminates drawbacks related to the overproliferation of fibroblasts and the subsequent disruption of tissue architecture, integrity, or function. Coculture of mouse pancreatic islets with senescent fibroblasts and endothelial cells in a gel matrix maintains the viability and function of islets ex vivo for up to five days. Applying senescent fibroblasts to wound repair in vivo leads to increased blood flow in a diabetic mouse model. Together, this work points to a new direction for modeling the delivery of cytokines and growth factors that promote microvascular tissue engineering and tissue repairs.
机译:摘要 细胞因子和生长因子的控制递送一直是分子和细胞生物工程、免疫治疗和再生医学研究的热门领域。这项研究表明,化学诱导衰老(细胞周期停滞)的原代人肺成纤维细胞可以作为活体来源,暂时产生促进血管生成或血管生成的必需因子,例如血管内皮生长因子 (VEGF)、肝细胞生长因子 (HGF) 和白细胞介素 8 (IL-8)。衰老成纤维细胞与人脐静脉内皮细胞在纤维蛋白凝胶中的共培养表明,微血管网络最早可在三天内加速形成和成熟。与使用非衰老成纤维细胞作为血管生成促进细胞不同,这种方法消除了与成纤维细胞过度增殖以及随后破坏组织结构、完整性或功能相关的缺点。小鼠胰岛与衰老成纤维细胞和内皮细胞在凝胶基质中共培养,可使胰岛的活力和功能在体外保持长达五天。在体内应用衰老成纤维细胞进行伤口修复会导致糖尿病小鼠模型中的血流量增加。总之,这项工作为模拟促进微血管组织工程和组织修复的细胞因子和生长因子的递送指明了新的方向。

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