Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center of Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center of Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China.
Cytokine Growth Factor Rev. 2022 Aug;66:53-73. doi: 10.1016/j.cytogfr.2022.05.003. Epub 2022 May 28.
To date, the wide application of cell-based biomaterials in tissue engineering and regeneration is remarkably hampered by immune rejection. Reducing the immunogenicity of cell-based biomaterials has become the latest direction in biomaterial research. Recently, genetically modified cell-based biomaterials with immunomodulatory genes have become a feasible solution to the immunogenicity problem. In this review, recent advances and future challenges of genetically modified immunomodulatory cell-based biomaterials are elaborated, including fabrication approaches, mechanisms of common immunomodulatory genes, application and, more importantly, current preclinical and clinical advances. The fabrication approaches can be categorized into commonly used (e.g., virus transfection) and newly developed approaches. The immunomodulatory mechanisms of representative genes involve complicated cell signaling pathways and metabolic activities. Wide application in curing multiple end-term diseases and replacing lifelong immunosuppressive therapy in multiple cell and organ transplantation models is demonstrated. Most significantly, practices of genetically modified organ transplantation have been conducted on brain-dead human decedent and even on living patients after a series of experiments on nonhuman primates. Nevertheless, uncertain biosecurity, nonspecific effects and overlooked personalization of current genetically modified immunomodulatory cell-based biomaterials are shortcomings that remain to be overcome.
迄今为止，细胞基生物材料在组织工程和再生中的广泛应用受到免疫排斥的显著阻碍。降低细胞基生物材料的免疫原性已成为生物材料研究的最新方向。最近，具有免疫调节基因的基因修饰细胞基生物材料已成为解决免疫原性问题的一种可行方法。在这篇综述中，阐述了基因修饰免疫调节细胞基生物材料的最新进展和未来挑战，包括制备方法、常见免疫调节基因的作用机制、应用，更重要的是，当前的临床前和临床进展。制备方法可分为常用方法（如病毒转染）和新开发的方法。代表性基因的免疫调节机制涉及复杂的细胞信号通路和代谢活动。广泛应用于治疗多种终末期疾病，并在多种细胞和器官移植模型中替代终身免疫抑制治疗。最重要的是，在一系列非人类灵长类动物实验之后，对脑死亡的人类死者甚至对活体患者进行了基因修饰器官移植的实践。然而，目前基因修饰免疫调节细胞基生物材料的生物安全性不确定、非特异性作用和个性化考虑不足等缺点仍然有待克服。
