Perfusion improves tissue architecture of engineered cardiac muscle
Perfusion improves tissue architecture of engineered cardiac muscle
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DOI：
10.1089/107632702753724950
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发表时间：
2002-04-01
影响因子：
--
通讯作者：
Vunjak-Novakovic, G
中科院分区：
文献类型：
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作者：
Carrier, RL;Rupnick, M;Vunjak-Novakovic, G
具有一定阈值厚度、组织结构均匀性和功能性的心肌将扩大目前可用于患有先天性或获得性心脏缺陷的患者的治疗选择。在充分混合的培养基中培养的心脏结构在相对无细胞的内部周围具有约100 μ m厚的外周组织样区域，该结构与组织内存在的浓度梯度一致。我们假设直接灌注培养的结构可以减少质量运输的扩散距离，改善细胞微环境中的氧、pH、营养物质和代谢物的控制，从而增加工程化心肌的厚度和空间均匀性。为了验证这一假设，构建体（9.5毫米直径，2毫米厚的光盘）的基础上，新生大鼠心肌细胞和纤维聚乙醇酸支架培养直接灌注培养基或在控制转瓶。灌注改善了细胞分布的空间均匀性，并增强了心脏特异性标志物的表达，这可能是由于对形成组织内局部微环境条件的控制得到了改善。因此，可以利用介质灌注来更好地模拟天然心肌内的运输条件，并且能够体外工程化具有临床上有用的厚度的心脏构建体。
Cardiac muscle with a certain threshold thickness, uniformity of tissue architecture, and functionality would expand the therapeutic options currently available to patients with congenital or acquired cardiac defects. Cardiac constructs cultured in well-mixed medium had an approximately 100-mum-thick peripheral tissue-like region around a relatively cell-free interior, a structure consistent with the presence of concentration gradients within the tissue. We hypothesized that direct perfusion of cultured constructs can reduce diffusional distances for mass transport, improve control of oxygen, pH, nutrients and metabolites in the cell microenvironment, and thereby increase the thickness and spatial uniformity of engineered cardiac muscle. To test this hypothesis, constructs (9.5-mm-diameter, 2-mm-thick discs) based on neonatal rat cardiac myocytes and fibrous polyglycolic acid scaffolds were cultured either directly perfused with medium or in control spinner flasks. Perfusion improved the spatial uniformity of cell distribution and enhanced the expression of cardiac-specific markers, presumably due to the improved control of local microenvironmental conditions within the forming tissue. Medium perfusion could thus be utilized to better mimic the transport conditions within native cardiac muscle and enable in vitro engineering of cardiac constructs with clinically useful thicknesses.