Determinants of Implantation Success in Pancreatic Cancer Patient-Derived Xenografts: Role of Matrigel Application, Histological Subtype, and Time Management

Abstract

Pancreatic cancer (PC) is a growing global health concern, highlighting the need for improved preclinical models. Patient-derived xenografts (PDXs) closely replicate tumor biology and serve as a vital link between preclinical and clinical research. This study investigated the key factors influencing the success of PDX implantation in PC. We compared Matrigel-assisted implantation versus Matrigel-free implantation. We also evaluated the impact of histological subtype on implantation success, analyzing pancreatic ductal adenocarcinoma (PDAC), adenosquamous carcinoma (ASPC), and acinar cell carcinoma (ACC). Additionally, we assessed whether the tumor specimen culture-to-implantation period affected both the take rate and tumor growth rate. A significance threshold of p < 0.05 was applied (95% confidence interval), and multivariable regression analysis was conducted to identify independent predictors of implantation success. In both NOD/SCID and NU/NU (nude) strains, Matrigel-assisted PDAC implantations achieved significantly higher take rates (75% vs. 90%) compared to direct implantations (25% vs. 0%) in the second generation (p = 0.02). The ASPC subtype was a significant predictor of success in the NOD/SCID strain (p = 0.04). The culture-to-implantation period did not affect take rates. The nude strain significantly prolonged ACC engraftment (p = 0.02). In direct ACC implantations, earlier generations (F1-F5) required shorter engraftment growth duration (p < 0.0001). For ASPC, later generations demonstrated longer growth duration (p < 0.04). These findings emphasize critical variables in optimizing PC PDX protocols, particularly Matrigel use, mouse strain selection, and consideration of histological and generation-specific effects. Such refinements can optimize PDX efficiency and translational relevance.