NTU-Technion Biomedical Labs, School of Materials Science and Engineering, Division of Materials Technology, Nanyang Technological University, Singapore, Singapore.
Tissue Eng Part A. 2013 May;19(9-10):1155-64. doi: 10.1089/ten.TEA.2012.0507. Epub 2013 Jan 16.
In most tissue engineering applications, understanding the factors affecting the growth dynamics of coculture systems is crucial for directing the population toward a desirable regenerative process. Yet, no comprehensive analysis method exists to quantify coculture population dynamics, let alone, a unifying model addressing the "environmental" factors influencing cell growth, all together. Here we suggest a modification of the Lotka-Volterra model to analyze the population dynamics of cocultured cells and predict their growth profiles for tissue engineering applications. This model, commonly used to describe the population dynamics of a prey and predator sharing a closed ecological niche, was found to fit our empirical data on cocultures of endothelial cells (ECs) and mesenchymal stem cells (MSCs) that have been widely investigated for their regenerative potential. Applying this model to cocultures of this sort allows us to quantify the effect that culturing conditions have on the way cell growth is affected by the same cells or by the other cells in the coculture. We found that in most cases, EC growth was inhibited by the same cells but promoted by MSCs. The principles resulting from this analysis can be used in various applications to guide the population toward a desired direction while shedding new light on the fundamental interactions between ECs and MSCs. Similar results were also demonstrated on complex substrates made from decellularized porcine cardiac extracellular matrix, where growth occurred only after coculturing ECs and MSCs together. Finally, this unique implementation of the Lotka-Volterra model may also be regarded as a roadmap for using such models with other potentially regenerative cocultures in various applications.
在大多数组织工程应用中，了解影响共培养体系生长动力学的因素对于指导细胞群体向期望的再生过程发展至关重要。然而，目前还没有一种全面的分析方法来量化共培养群体动力学，更不用说建立一个统一的模型来描述影响细胞生长的“环境”因素了。在这里，我们建议对洛特卡-沃尔泰拉模型进行修改，以分析共培养细胞的群体动力学，并预测它们在组织工程应用中的生长曲线。该模型通常用于描述在封闭生态位中共存的猎物和捕食者的种群动态，我们发现它适用于广泛研究其再生潜力的内皮细胞（ECs）和间充质干细胞（MSCs）共培养的经验数据。将该模型应用于此类共培养中，可以量化培养条件对细胞生长的影响方式，这些影响既可以来自同一细胞，也可以来自共培养中的其他细胞。我们发现，在大多数情况下，EC 的生长受到相同细胞的抑制，但受到 MSCs 的促进。从这种分析中得出的原则可以应用于各种应用中，以引导群体向期望的方向发展，同时为 ECs 和 MSCs 之间的基本相互作用提供新的认识。在由脱细胞猪心脏细胞外基质制成的复杂基质上也得到了类似的结果，只有在共培养 ECs 和 MSCs 后才会发生生长。最后，这种对洛特卡-沃尔泰拉模型的独特应用也可以被视为在各种应用中使用这种模型与其他潜在的再生共培养的路线图。
