Department of Medicine, University of Otago, Dunedin 9016, New Zealand.
Department of Medicine, University of Auckland, Grafton, Auckland 1024, New Zealand; Adult Emergency Department, Auckland City Hospital, Auckland District Health Board, Grafton, Auckland, 1023, New Zealand.
Acta Biomater. 2021 Oct 1;133:102-113. doi: 10.1016/j.actbio.2021.05.049. Epub 2021 May 31.
Tissue engineered heart valves may one day offer an exciting alternative to traditional valve prostheses. Methods of construction vary, from decellularised animal tissue to synthetic hydrogels, but the goal is the same: the creation of a 'living valve' populated with autologous cells that may persist indefinitely upon implantation. Previous failed attempts in humans have highlighted the difficulty in predicting how a novel heart valve will perform in vivo. A significant hurdle in bringing these prostheses to market is understanding the immune reaction in the short and long term. With respect to innate immunity, the chronic remodelling of a tissue engineered implant by macrophages remains poorly understood. Also unclear are the mechanisms behind unknown antigens and their effect on the adaptive immune system. No silver bullet exists, rather researchers must draw upon a number of in vitro and in vivo models to fully elucidate the effect a host will exert on the graft. This review details the methods by which the immunogenicity of tissue engineered heart valves may be investigated and reveals areas that would benefit from more research. STATEMENT OF SIGNIFICANCE: Both academic and private institutions around the world are committed to the creation of a valve prosthesis that will perform safely upon implantation. To date, however, no truly non-immunogenic valves have emerged. This review highlights the importance of preclinical immunogenicity assessment, and summarizes the available techniques used in vitro and in vivo to elucidate the immune response. To the authors knowledge, this is the first review that details the immune testing regimen specific to a TEHV candidate.
组织工程心脏瓣膜有朝一日可能成为传统瓣膜假体的一个令人兴奋的替代方案。其构建方法多种多样，从去细胞化的动物组织到合成水凝胶，但目标是相同的：创建一个“活的瓣膜”，其中充满了自体细胞，这些细胞在植入后可能会无限期地存在。以前在人类中失败的尝试突显了预测新型心脏瓣膜在体内性能的困难。将这些假体推向市场的一个重大障碍是了解短期和长期内的免疫反应。就先天免疫而言，巨噬细胞对组织工程植入物的慢性重塑仍然知之甚少。未知抗原背后的机制及其对适应性免疫系统的影响也不清楚。没有银弹，而是研究人员必须利用许多体外和体内模型来充分阐明宿主对移植物的影响。这篇综述详细介绍了研究组织工程心脏瓣膜免疫原性的方法，并揭示了需要更多研究的领域。重要性声明：世界各地的学术和私人机构都致力于创造一种安全植入后即可发挥作用的瓣膜假体。然而，迄今为止，还没有真正的非免疫原性瓣膜出现。这篇综述强调了临床前免疫原性评估的重要性，并总结了用于体外和体内阐明免疫反应的现有技术。据作者所知，这是第一篇详细介绍针对 TEHV 候选物的免疫测试方案的综述。
