IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain.
Tissue Eng Part A. 2013 Aug;19(15-16):1665-74. doi: 10.1089/ten.TEA.2012.0661. Epub 2013 Apr 19.
Clinical therapies have traditionally been developed using two-dimensional (2D) cell culture systems, which fail to accurately capture tissue complexity. Therefore, three-dimensional (3D) cell cultures are more attractive platforms to integrate multiple cues that arise from the extracellular matrix and cells, closer to an in vivo scenario. Here we report the development of a 3D cellular model for the in vitro assessment of the outcome of oxygen- and drug-dependent therapies, exemplified by photodynamic therapy (PDT). Using a synthetic self-assembling peptide as a cellular scaffold (RAD16-I), we were able to recreate the in vivo limitation of oxygen and drug diffusion and its biological effect, which is the development of cellular resistance to therapy. For the first time, the production and decay of the cytotoxic species singlet oxygen could be observed in a 3D cell culture. Results revealed that the intrinsic mechanism of action is maintained in both systems and, hence, the dynamic mass transfer effects accounted for the major differences in efficacy between the 2D and 3D models. We propose that this methodological approach will help to improve the efficacy of future oxygen- and drug-dependent therapies such as PDT.
临床治疗方法传统上是使用二维（2D）细胞培养系统开发的，该系统无法准确捕捉组织的复杂性。因此，三维（3D）细胞培养更具吸引力，因为它可以整合来自细胞外基质和细胞的多种信号，更接近体内情况。在这里，我们报告了一种用于体外评估氧依赖性和药物依赖性治疗结果的 3D 细胞模型的开发，以光动力疗法（PDT）为例。使用合成自组装肽作为细胞支架（RAD16-I），我们能够重现体内氧和药物扩散及其生物学效应的限制，即细胞对治疗的抗性发展。这是首次在 3D 细胞培养中观察到细胞毒性物质单线态氧的产生和衰减。结果表明，两种系统中均保持了内在的作用机制，因此，动态质量传递效应解释了 2D 和 3D 模型之间疗效的主要差异。我们提出，这种方法将有助于提高光动力疗法等未来氧依赖性和药物依赖性治疗的疗效。
