Abstract
Gestational trophoblastic diseases (GTDs) are a group of diseases characterized by abnormal cellular proliferation of atypical trophoblasts. A hydatidiform mole is an abnormal pregnancy caused by genetic fertilization disorders, and it can be classified as a complete hydatidiform mole (CHM) or a partial hydatidiform mole. The aim of this study was to establish cell lines from CHMs and to characterize the cells for future studies concerning GTD. HMol1-2C, HMol1-3B, HMol1-8 and HMol3-1B were established from primary cultures of CHM explants following the introduction of different combinations of genes including human telomerase reverse transcriptase (hTERT), a mutant form of CDK (CDK4R24C), cyclin D1, p53C234, MYC and HRAS. HMol1-2C, HMol1-3B, and HMol3-1B were confirmed to originate from trophoblasts of androgenic, homozygous CHMs. These three cell lines exhibited low human chorionic gonadotropin secretion, low migration and invasion abilities, and the potential to differentiate into syncytiotrophoblastic cells via forskolin treatment. These results suggest that these cells exhibit characteristics of trophoblastic cells, especially cytotrophoblastic cells. HMol1-8 was found to consist of diploid cells and originated from maternal cells, suggesting that they were derived from decidual cells. In conclusion, we successfully established three cell lines from CHMs by introduction of hTERT and other genes. Analysis revealed that the genetic origin of each cell line was identical with that of the original molar tissue, and the cell lines exhibited characteristics of trophoblastic cells, which are similar to undifferentiated cytotrophoblasts.