Institute for Medical Physics and Biophysics, Faculty of Medicine, University of Leipzig , 04107 Leipzig, Germany.
Institute of Virology, University of Leipzig , 04103 Leipzig, Germany.
ACS Nano. 2016 Jul 26;10(7):6563-73. doi: 10.1021/acsnano.6b00999. Epub 2016 Jul 5.
Induced pluripotent stem cells (iPSCs) have the ability to differentiate into any specialized somatic cell type, which makes them an attractive tool for a wide variety of scientific approaches, including regenerative medicine. However, their pluripotent state and their growth in compact colonies render them difficult to access and, therefore, restrict delivery of specific agents for cell manipulation. Thus, our investigation focus was set on the evaluation of the capability of layer-by-layer (LbL) designed microcarriers to serve as a potential drug delivery system to iPSCs, as they offer several appealing advantages. Most notably, these carriers allow for the transport of active agents in a protected environment and for a rather specific delivery through surface modifications. As we could show, charge and mode of LbL carrier application as well as the size of the iPSC colonies determine the interaction with and the uptake rate by iPSCs. None of the examined conditions had an influence on iPSC colony properties such as colony morphology and size or maintenance of pluripotent properties. An overall interaction rate of LbL carriers with iPSCs of up to 20% was achieved. Those data emphasize the applicability of LbL carriers for stem cell research. Additionally, the potential use of LbL carriers as a promising delivery tool for iPSCs was contrasted to viral particles and liposomes. The identified differences among those delivery tools have substantiated our major conclusion that LbL carrier uptake rate is influenced by characteristic features of the iPSC colonies (most notably colony size) in addition to their surface charges.
诱导多能干细胞(iPSCs)具有分化为任何特化体细胞类型的能力,这使它们成为广泛的科学方法,包括再生医学的有吸引力的工具。然而,它们的多能状态和它们在紧凑集落中的生长使得它们难以接近,因此限制了特定细胞操作试剂的传递。因此,我们的研究重点是评估层层(LbL)设计的微载体作为 iPSCs 的潜在药物传递系统的能力,因为它们具有许多吸引人的优点。最值得注意的是,这些载体允许在受保护的环境中运输活性剂,并通过表面修饰进行相当特定的递送。正如我们所展示的,LbL 载体的电荷和应用模式以及 iPSC 集落的大小决定了与 iPSC 的相互作用和摄取速率。所检查的条件均未对 iPSC 集落的性质(如集落形态和大小或多能性的维持)产生影响。LbL 载体与 iPSC 的总体相互作用率高达 20%。这些数据强调了 LbL 载体在干细胞研究中的适用性。此外,还将 LbL 载体作为 iPSC 的有前途的传递工具的潜在用途与病毒颗粒和脂质体进行了对比。这些传递工具之间的差异证实了我们的主要结论,即 LbL 载体的摄取率除了表面电荷外,还受到 iPSC 集落的特征(尤其是集落大小)的影响。