Jara Avaca Monica, Gruh Ina
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department for Cardiothoracic, Vascular and Transplantation Surgery (HTTG), Hannover Medical School (MHH) & Cluster of Excellence REBIRTH, Hannover, Germany.
Adv Biochem Eng Biotechnol. 2018;163:117-146. doi: 10.1007/10_2017_24.
Engineered cardiac tissue might enable novel therapeutic strategies for the human heart in a number of acquired and congenital diseases. With recent advances in stem cell technologies, namely the availability of pluripotent stem cells, the generation of potentially autologous tissue grafts has become a realistic option. Nevertheless, a number of limitations still have to be addressed before clinical application of engineered cardiac tissue based on human stem cells can be realized. We summarize current progress and pending challenges regarding the optimal cell source, cardiomyogenic lineage specification, purification, safety of genetic cell engineering, and genomic stability. Cardiac cells should be combined with clinical grade scaffold materials for generation of functional myocardial tissue in vitro. Scale-up to clinically relevant dimensions is mandatory, and tissue vascularization is most probably required both for preclinical in vivo testing in suitable large animal models and for clinical application. Graphical Abstract.
工程化心肌组织可能为多种获得性和先天性心脏病提供新的治疗策略。随着干细胞技术的最新进展,即多能干细胞的可得性,生成潜在的自体组织移植物已成为一个现实的选择。然而,在基于人类干细胞的工程化心肌组织能够实现临床应用之前,仍有许多限制需要解决。我们总结了目前在最佳细胞来源、心肌细胞谱系定向分化、纯化、基因细胞工程的安全性以及基因组稳定性方面的进展和悬而未决的挑战。心脏细胞应与临床级支架材料相结合,以在体外生成功能性心肌组织。扩大到临床相关尺寸是必不可少的,并且无论是在合适的大型动物模型中进行临床前体内测试还是临床应用,组织血管化很可能都是必需的。图形摘要。