基质凝胶
血管生成
细胞生物学
成纤维细胞生长因子
新生血管
组织工程
碱性成纤维细胞生长因子
生物
生长因子
化学
生物化学
癌症研究
受体
遗传学
作者
Gal Chen,Rotem Levin,Shira Landau,Maya Kaduri,Omer Adir,Iris Ianovici,Nitzan Krinsky,Ofri Doppelt-Flikshtain,Jeny Shklover,Janna Shainsky‐Roitman,Shulamit Levenberg,Avi Schroeder
标识
DOI:10.1073/pnas.2207525119
摘要
Progress in bottom-up synthetic biology has stimulated the development of synthetic cells (SCs), autonomous protein-manufacturing particles, as dynamic biomimetics for replacing diseased natural cells and addressing medical needs. Here, we report that SCs genetically encoded to produce proangiogenic factors triggered the physiological process of neovascularization in mice. The SCs were constructed of giant lipid vesicles and were optimized to facilitate enhanced protein production. When introduced with the appropriate genetic code, the SCs synthesized a recombinant human basic fibroblast growth factor (bFGF), reaching expression levels of up to 9⋅10 6 protein copies per SC. In culture, the SCs induced endothelial cell proliferation, migration, tube formation, and angiogenesis-related intracellular signaling, confirming their proangiogenic activity. Integrating the SCs with bioengineered constructs bearing endothelial cells promoted the remodeling of mature vascular networks, supported by a collagen-IV basement membrane–like matrix. In vivo, prolonged local administration of the SCs in mice triggered the infiltration of blood vessels into implanted Matrigel plugs without recorded systemic immunogenicity. These findings emphasize the potential of SCs as therapeutic platforms for activating physiological processes by autonomously producing biological drugs inside the body.
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