Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue
Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue
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DOI：
10.1002/bit.20722
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发表时间：
2006-02-05
影响因子：
3.8
通讯作者：
Vunjak-Novakovic, G
中科院分区：
文献类型：
--
作者：
Radisic, M;Malda, J;Vunjak-Novakovic, G
为了临床应用，心脏移植物应该是厚的和紧凑的，并且含有生理密度的代谢活性的分化细胞。这涉及到需要控制整个构造体积中的营养素水平，最重要的是氧气水平。大多数培养系统涉及结构内的扩散运输，这种情况与氧浓度、细胞密度、细胞活力和功能的梯度有关。我们研究的目的是测量静态培养的心脏结构中氧的扩散梯度，并将氧梯度与细胞数量和细胞活力的空间分布相关联。使用微电极，我们测量了氧分布在一个圆盘形的结构（3.6毫米直径，1.8毫米厚）的基础上，在胶原支架上培养16天的新生大鼠心肌细胞在静态培养皿。为了使实验数据合理化，推导出氧分布的数学模型作为构建体内的细胞密度、活力和空间位置的函数。氧浓度和细胞活力线性下降，活细胞密度随着离构建体表面的距离呈指数下降。活细胞的生理密度仅存在于构建体厚度的前128 μ m内。培养基流量显著增加了构建体内的氧浓度，这与在对流混合生物反应器中培养的构建体观察到的改善的组织性质相关。(c)2005 Wiley Periodicals，Inc.
For clinical utility, cardiac grafts should be thick and compact, and contain physiologic density of metabolically active, differentiated cells. This involves the need to control the levels of nutrients, and most critically oxygen, throughout the construct volume. Most culture systems involve diffusional transport within the constructs, a situation associated with gradients of oxygen concentration, cell density, cell viability, and function. The goal of our study was to measure diffusional gradients of oxygen in statically cultured cardiac constructs, and to correlate oxygen gradients to the spatial distributions of cell number and cell viability. Using microelectrodes, we measured oxygen distribution in a disc-shaped constructs (3.6 mm diameter, 1.8 mm thickness) based on neonatal rat cardiomyocytes cultured on collagen scaffolds for 16 days in static dishes. To rationalize experimental data, a mathematical model of oxygen distribution was derived as a function of cell density, viability, and spatial position within the construct. Oxygen concentration and cell viability decreased linearly and the live cell density decreased exponentially with the distance from the construct surface. Physiological density of live cells was present only within the first 128 mu m of the construct thickness. Medium flow significantly increased oxygen concentration within the construct, correlating with the improved tissue properties observed for constructs cultured in convectively mixed bioreactors. (c) 2005 Wiley Periodicals, Inc.