Research Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
PLoS One. 2020 May 22;15(5):e0233647. doi: 10.1371/journal.pone.0233647. eCollection 2020.
In response to injury, adult Schwann cells (SCs) re-enter the cell cycle, change their expression profile, and exert repair functions important for wound healing and the re-growth of axons. While this phenotypical instability of SCs is essential for nerve regeneration, it has also been implicated in cancer progression and de-myelinating neuropathies. Thus, SCs became an important research tool to study the molecular mechanisms involved in repair and disease and to identify targets for therapeutic intervention. A high purity of isolated SC cultures used for experimentation must be demonstrated to exclude that novel findings are derived from a contaminating fibroblasts population. In addition, information about the SC proliferation status is an important parameter to be determined in response to different treatments. The evaluation of SC purity and proliferation, however, usually depends on the time consuming, manual assessment of immunofluorescence stainings or comes with the sacrifice of a large amount of SCs for flow cytometry analysis. We here show that rat SC culture derived cytospins stained for SC marker SOX10, proliferation marker EdU, intermediate filament vimentin and DAPI allowed the determination of SC identity and proliferation by requiring only a small number of cells. Furthermore, the CellProfiler software was used to develop an automated image analysis pipeline that quantified SCs and proliferating SCs from the obtained immunofluorescence images. By comparing the results of total cell count, SC purity and SC proliferation rate between manual counting and the CellProfiler output, we demonstrated applicability and reliability of the established pipeline. In conclusion, we here combined the cytospin technique, a multi-colour immunofluorescence staining panel, and an automated image analysis pipeline to enable the quantification of SC purity and SC proliferation from small cell aliquots. This procedure represents a solid read-out to simplify and standardize the quantification of primary SC culture purity and proliferation.
针对损伤,成年雪旺细胞(SCs)重新进入细胞周期,改变其表达谱,并发挥修复功能,这对于伤口愈合和轴突的再生非常重要。虽然SCs 的这种表型不稳定对于神经再生是必不可少的,但它也与癌症进展和脱髓鞘神经病变有关。因此,SCs 成为研究涉及修复和疾病的分子机制以及鉴定治疗干预靶点的重要研究工具。必须证明用于实验的分离SCs 培养物的高纯度,以排除新发现源自污染的成纤维细胞群体。此外,SCs 增殖状态的信息是对不同处理作出反应时需要确定的一个重要参数。然而,SCs 纯度和增殖的评估通常取决于耗时的、手动评估免疫荧光染色,或者需要牺牲大量的SCs 用于流式细胞术分析。我们在这里展示,用于 SOX10、增殖标志物 EdU、中间丝波形蛋白和 DAPI 染色的大鼠SCs 培养物衍生的细胞涂片,可以通过仅需要少量细胞来确定SCs 的身份和增殖。此外,使用 CellProfiler 软件开发了一种自动化的图像分析管道,可以从获得的免疫荧光图像中定量SCs 和增殖的SCs。通过比较手动计数和 CellProfiler 输出的总细胞计数、SCs 纯度和SCs 增殖率的结果,我们证明了所建立的管道的适用性和可靠性。总之,我们在这里将细胞涂片技术、多色免疫荧光染色面板和自动化图像分析管道相结合,实现了从小细胞样本中定量SCs 纯度和SCs 增殖的功能。该程序是简化和标准化原代SCs 培养物纯度和增殖定量的可靠方法。