Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien.
Tzu Chi University, Hualien.
Cell Transplant. 2023 Jan-Dec;32:9636897231160216. doi: 10.1177/09636897231160216.
Fallopian tube epithelial cells (FTEC) are thought to be the cell of origin of high-grade serous ovarian carcinoma. FTEC organoids can be used as research models for the disease. Nevertheless, culturing organoids requires a medium supplemented with several expensive growth factors. We proposed that a combined conditioned medium based on the composition of the fallopian tubes, including epithelial, stromal, and endothelial cells could enhance FTEC organoid formation. We derived two primary culture cell lines from the fimbria portion of the fallopian tubes. The organoids were split into conventional or combined medium groups based on what medium they were grown in and compared. The number and size of the organoids were evaluated. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to evaluate gene and protein expression (PAX8, FOXJ1, beta-catenin, and stemness genes). Enzyme-linked immunosorbent assay was used to measure Wnt3a and RSPO1 in both mediums. DKK1 and LiCl were added to the mediums to evaluate their influence on beta-catenin signaling. The growth factor in the combined medium was evaluated by the growth factor array. We found that the conventional medium was better for organoids regarding proliferation (number and size). In addition, WNT3A and RSPO1 concentrations were too low in the combined medium and needed to be added making the cost equivalent to the conventional medium. However, the organoid formation rate was 100% in both groups. Furthermore, the combined medium group had higher PAX8 and stemness gene expression (OLFM4, SSEA4, LGR5, B3GALT5) when compared with the conventional medium group. Wnt signaling was evident in the organoids grown in the conventional medium but not in the combined medium. PLGF, IGFBP6, VEGF, bFGF, and SCFR were found to be enriched in the combined medium. In conclusion, the combined medium could successfully culture organoids and enhance PAX8 and stemness gene expression. However, the conventional medium was a better medium for organoid proliferation. The expense of both mediums was comparable. The benefit of using a combined medium requires further exploration.
输卵管上皮细胞(FTEC)被认为是高级别浆液性卵巢癌的起源细胞。FTEC 类器官可作为该疾病的研究模型。然而,培养类器官需要一种添加了几种昂贵生长因子的培养基。我们提出,一种基于输卵管组成的组合条件培养基,包括上皮细胞、基质细胞和内皮细胞,可以增强 FTEC 类器官的形成。我们从输卵管的伞部分离出两个原代培养细胞系。类器官根据生长的培养基分为常规或组合培养基组,并进行比较。评估类器官的数量和大小。使用定量聚合酶链反应(qPCR)和免疫组织化学(IHC)评估基因和蛋白表达(PAX8、FOXJ1、β-连环蛋白和干性基因)。酶联免疫吸附试验用于测量两种培养基中的 Wnt3a 和 RSPO1。向培养基中添加 DKK1 和 LiCl 以评估它们对 β-连环蛋白信号的影响。通过生长因子阵列评估组合培养基中的生长因子。我们发现常规培养基在类器官的增殖(数量和大小)方面更好。此外,组合培养基中的 WNT3A 和 RSPO1 浓度太低,需要添加,使得成本与常规培养基相当。然而,两组类器官的形成率均为 100%。此外,与常规培养基组相比,组合培养基组的 PAX8 和干性基因表达(OLFM4、SSEA4、LGR5、B3GALT5)更高。在常规培养基中生长的类器官中存在明显的 Wnt 信号,但在组合培养基中不存在。在组合培养基中发现 PLGF、IGFBP6、VEGF、bFGF 和 SCFR 富集。总之,组合培养基可以成功培养类器官并增强 PAX8 和干性基因表达。然而,常规培养基是类器官增殖的更好培养基。两种培养基的费用相当。使用组合培养基的好处需要进一步探索。