Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. Recent multi-omics studies revealed the promising targets for CCA treatment; however, limited models for drug discovery are available. This study aimed to develop a patient-derived xenograft (PDX) model as well as PDX-derived cell lines of CCA for future drug screening. From a total of 16 CCA frozen tissues, 75% (eight intrahepatic and four extrahepatic subtypes) were successfully grown and subpassaged in Balb/c Rag-2^-/-/Jak3^-/- mice. A shorter duration of PDX growth was observed during F0 to F2 transplantation; concomitantly, increased Oct-3/4 and Sox2 were evidenced in 50% and 33%, respectively, of serial PDXs. Only four cell lines were established. The cell lines exhibited either bile duct (KKK-D049 and KKK-D068) or combined hepatobiliary origin (KKK-D131 and KKK-D138). These cell lines acquired high transplantation efficiency in both subcutaneous (100%) and intrasplenic (88%) transplantation models. The subcutaneously transplanted xenograft retained the histological architecture as in the patient tissues. Our models of CCA PDX and PDX-derived cell lines would be a useful platform for CCA precision medicine.

The hill tribes of northern Thailand comprise nine officially recognized groups: the Austroasiatic-speaking (AA) Khmu, Htin and Lawa; the Hmong-Mien-speaking (HM) IuMien and Hmong; and the Sino-Tibetan-speaking (ST) Akha, Karen, Lahu and Lisu. Except the Lawa, the rest of the hill tribes migrated into their present habitats only very recently. The Thai hill tribes were of much interest to research groups focusing on study of cultural and genetic variation because of their unique languages and cultures. So far, there have been several genetic studies of the Thai hill tribes. However, complete forensic microsatellite database of the Thai hill tribes is still lacking. To construct such database, we newly generated 654 genotypes of 15 microsatellites commonly used in forensic investigation that belong to all the nine hill tribes and also non-hill tribe highlanders from northern Thailand. We also combined 329 genotypes from previous studies of northern Thai populations bringing to a total of 983 genotypes, which were then subjected to genetic structure and population relationships analyses. Our overall results indicated homogenous genetic structure within the HM- and Tai-Kadai (TK)-speaking groups, large genetic divergence of the HM-speaking Hmong but not IuMien from the other Thai groups, and genetic heterogeneity within the ST- and AA-speaking groups, reflecting different population interactions and admixtures. In addition to establishing genetic relationships within and among these populations, our finding, which provides a more complete picture of the forensic microsatellite database of the multiple Thai highland dwellers, would not only serve to expand and strengthen forensic investigation in Thailand, but would also benefit its neighboring countries of Laos and Myanmar, from which many of the Thai hill tribes originated and where large populations of these ethnic groups still reside.