Tao Ze-Wei, Mohamed Mohamed, Hogan Matthew, Salazar Betsy, Patel Nikita M, Birla Ravi K
From the Department of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, Texas.
ASAIO J. 2015 Jul-Aug;61(4):429-36. doi: 10.1097/MAT.0000000000000233.
There is a chronic shortage of donor hearts. The ability to fabricate complete bioartificial hearts (BAHs) may be an alternative solution. The current study describes a method to support the fabrication and culture of BAHs. Rat hearts were isolated and subjected to a detergent based decellularization protocol to remove all cellular components, leaving behind an intact extracellular matrix. Primary cardiac cells were isolated from neonatal rat hearts, and direct cell transplantation was used to populate the acellular scaffolds. Bioartificial hearts were maintained in a custom fabrication gravity fed perfusion culture system to support media delivery. The functional performance of BAHs was assessed based on left ventricle pressure and on electrocardiogram. Furthermore, BAHs were sectioned and stained for the whole heart cardiac tissue distribution and for cardiac molecules, such as α-actinin, cardiac troponin I, collagen type I, connexin 43, von Willebrand factor, and ki67. Bioartificial hearts replicated a partial subset of properties of natural rat hearts. The current study provided a method for fabrication of a BAH and revealed challenges toward BAH fabrication with functional performance metrics of natural mammalian hearts.
供体心脏长期短缺。制造完整的生物人工心脏(BAH)或许是一种替代解决方案。当前研究描述了一种支持生物人工心脏制造和培养的方法。分离大鼠心脏,并采用基于去污剂的去细胞方案去除所有细胞成分,留下完整的细胞外基质。从新生大鼠心脏中分离出原代心肌细胞,并通过直接细胞移植使脱细胞支架重新细胞化。生物人工心脏置于定制制造的重力灌注培养系统中以支持培养基输送。基于左心室压力和心电图评估生物人工心脏的功能性能。此外,对生物人工心脏进行切片,并对整个心脏的心肌组织分布以及心肌分子(如α - 辅肌动蛋白、心肌肌钙蛋白I、I型胶原蛋白、连接蛋白43、血管性血友病因子和Ki67)进行染色。生物人工心脏复制了天然大鼠心脏部分属性。当前研究提供了一种制造生物人工心脏的方法,并揭示了在以天然哺乳动物心脏功能性能指标制造生物人工心脏方面所面临的挑战。