Guhathakurta Soma, Mathapati Santosh, Bishi Dillip Kumar, Rallapalli Suneel, Cherian Kotturathu Mammen
Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India
International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai, India.
Asian Cardiovasc Thorac Ann. 2014 Oct;22(8):935-43. doi: 10.1177/0218492314523627. Epub 2014 Feb 18.
This study aimed to create a myocardial tissue construct by tissue engineering to repair, replace, and regenerate damaged cardiac tissue.
Human cardiac muscles harvested from a homograft heart retrieval system were decellularized followed by coating with electrospun nanofibers to make them amenable to scaffolding. These processed cardiac tissues were nourished in modified media having ischemic cardiac tissue conditioned media in 6 separate experimental variants, and cord blood mononuclear cells were injected into 4 of them. On the 17th day of culture, the nanofiber-coated scaffolds injected with mononuclear cells and/or reinforced by electrical and mechanical forces, started contracting spontaneously at varying rates, while the control remain noncontractile. Histological staining confirmed the pre-culture acellularity as well as post-culture stem cell viability, and revealed expression of troponin I and cardiac myosin. The acellular processed scaffold when implanted into sheep ischemic myocardial apex revealed transformation into sheep myocardium after 4 months of implantation.
These results provide direct evidence for the re-cellularization of decellularized cardiac tissue grafts reinforced with a polymer nanofiber coating, by human mononuclear cells injection, leading to generation of a tissue-engineered myocardial construct.
本研究旨在通过组织工程构建心肌组织,以修复、替代和再生受损的心脏组织。
从同种异体心脏回收系统获取的人类心肌组织进行脱细胞处理,随后用静电纺丝纳米纤维进行包被,使其适合作为支架。这些经过处理的心脏组织在含有缺血性心脏组织条件培养基的改良培养基中,按照6种不同的实验变体进行培养,其中4种注射了脐带血单个核细胞。在培养的第17天,注射了单个核细胞和/或受到电和机械力增强的纳米纤维包被支架开始以不同速率自发收缩,而对照组仍无收缩。组织学染色证实了培养前的无细胞状态以及培养后干细胞的活力,并显示了肌钙蛋白I和心肌肌球蛋白的表达。将脱细胞处理的支架植入绵羊缺血心肌心尖后,植入4个月后显示转变为绵羊心肌。
这些结果为通过注射人类单个核细胞使聚合物纳米纤维包被增强的脱细胞心脏组织移植物重新细胞化提供了直接证据,从而导致组织工程化心肌构建体的产生。