1 Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
2 Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
SLAS Technol. 2017 Dec;22(6):646-661. doi: 10.1177/2472630317726050. Epub 2017 Aug 21.
Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.
多能基质细胞（MSCs，通常称为间充质干细胞）因其据称能够分化为肌肉骨骼谱系而在再生医学领域引起了广泛关注。鉴于 MSC 群体的固有异质性，最近的研究表明，细胞形态可能是 MSC 分化潜力的指标。为了改进当前的方法并开发用于 MSC 形态评估的简单而有效的方法，我们将被动泵微流控技术与高维形态特征相结合，为标准化高通量分析提供了强大的工具。我们使用紫外线 (UV) 光作为可重复的聚苯乙烯基底修饰的方式，表明在包含暴露于 UV 的基底的微流控直通道装置上接种的 MSC 表现出与基底修饰程度相应的形态变化。基底修饰还使在微流道中以较低而不是较高密度接种的 MSC 发生更大的形态变化。尽管形态上存在很大的相似趋势，但在微尺度而非传统的宏观平台上接种的 MSC 对基底性质的变化表现出更高的敏感性。总之，我们改编并验证了包含简单直通道阵列的微流控细胞培养平台作为高通量定量形态分析的可行且强大的工具，用于研究细胞-材料相互作用。
