Fujita Buntaro, Zimmermann Wolfram-Hubertus
Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany.
Curr Cardiol Rep. 2017 Sep;19(9):78. doi: 10.1007/s11886-017-0892-4.
This review provides an overview of the current state of tissue-engineered heart repair with a special focus on the anticipated modes of action of tissue-engineered therapy candidates and particular implications as to transplant immunology.
Myocardial tissue engineering technologies have made tremendous advances in recent years. Numerous different strategies are under investigation and have reached different stages on their way to clinical translation. Studies in animal models demonstrated that heart repair requires either remuscularization by delivery of bona fide cardiomyocytes or paracrine support for the activation of endogenous repair mechanisms. Tissue engineering approaches result in enhanced cardiomyocyte retention and sustained remuscularization, but may also be explored for targeted paracrine or mechanical support. Some of the more advanced tissue engineering approaches are already tested clinically; others are at late stages of pre-clinical development. Process optimization towards cGMP compatibility and clinical scalability of contractile engineered human myocardium is an essential step towards clinical translation. Long-term allograft retention can be achieved under immune suppression. HLA matching may be an option to enhance graft retention and reduce the need for comprehensive immune suppression. Tissue-engineered heart repair is entering the clinical stage of the translational pipeline. Like in any effective therapy, side effects must be anticipated and carefully controlled. Allograft implantation under immune suppression is the most likely clinical scenario. Strategies to overcome transplant rejection are evolving and may further boost the clinical acceptance of tissue-engineered heart repair.
本综述概述了组织工程心脏修复的当前状况，特别关注组织工程治疗候选方案的预期作用模式以及移植免疫学的特殊影响。
近年来，心肌组织工程技术取得了巨大进展。众多不同策略正在研究中，并且在临床转化的道路上已达到不同阶段。动物模型研究表明，心脏修复需要通过递送真正的心肌细胞进行再肌化，或通过旁分泌支持激活内源性修复机制。组织工程方法可增强心肌细胞保留并持续进行再肌化，但也可探索用于靶向旁分泌或机械支持。一些更先进的组织工程方法已在临床上进行测试；其他方法处于临床前开发的后期阶段。朝着cGMP兼容性和收缩性工程化人心肌的临床可扩展性进行工艺优化是迈向临床转化的关键一步。在免疫抑制下可实现长期同种异体移植物保留。HLA匹配可能是增强移植物保留并减少全面免疫抑制需求的一种选择。组织工程心脏修复正在进入转化流程的临床阶段。与任何有效治疗一样，必须预期并仔细控制副作用。免疫抑制下的同种异体移植物植入是最可能的临床情况。克服移植排斥的策略正在不断发展，可能会进一步提高组织工程心脏修复的临床接受度。
