Department of Biology, Lakehead University, Thunder Bay ON, P7B 5E1, Canada.
Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, Thunder Bay ON, P7B 6V4, Canada.
Sci Rep. 2018 Dec 14;8(1):17869. doi: 10.1038/s41598-018-36150-4.
The successful isolation and propagation of patient-derived keratinocytes from cervical lesions constitute a more appropriate model of cervical disease than traditional cervical cancer-derived cell lines such as SiHa and CaSki. Our aim was to streamline the growth of patient-obtained, cervical keratinocytes into a reproducible process. We performed an observational case series study with 60 women referred to colposcopy for a diagnostic biopsy. Main outcome measures were how many samples could be passaged at least once (n = 11), and where enough cells could be established, to precisely define their proliferation profile over time (n = 3). Altering cell culture conditions over those reported by other groups markedly improved outcomes. We were also successful in making freeze backs which could be resuscitated to successfully propagate multi-layered, organoids from cervical keratinocytes (n = 3). For best results, biopsy-intrinsic factors such as size and tissue digestion appear to be major variables. This seems to be the first systematic report with a well characterized and defined sample size, detailed protocol, and carefully assessed cell yield and performance. This research is particularly impactful for constituting a sample repository-on-demand for appropriate disease modelling and drug screening under the umbrella of personalized health.
成功地从宫颈病变中分离和培养患者来源的角质形成细胞,比传统的宫颈癌衍生细胞系(如 SiHa 和 CaSki)更能模拟宫颈疾病。我们的目的是将患者获得的宫颈角质形成细胞的生长过程简化为可重复的过程。我们进行了一项观察性病例系列研究,纳入了 60 名因诊断性活检而转诊行阴道镜检查的女性。主要观察指标为至少传代一次的样本数量(n=11),以及能够建立足够数量细胞的样本数量,以精确确定其随时间的增殖情况(n=3)。改变细胞培养条件,明显优于其他研究组报道的条件,显著提高了结果。我们还成功地制作了冷冻备份,可复苏以成功地从宫颈角质形成细胞中增殖出多层类器官(n=3)。为了获得最佳结果,活检内在因素(如大小和组织消化)似乎是主要变量。这似乎是第一个系统报告,具有特征明确和定义明确的样本量、详细的方案以及仔细评估的细胞产量和性能。这项研究对于构成按需样本库具有特别重要的意义,可用于个性化健康领域的适当疾病建模和药物筛选。