A 3D in vitro model of endometrial cancer incorporating endothelial and endometrial cancer cells to facilitate drug screening analysis.
Background As the number of patients diagnosed with endometrial cancer keeps increasing, the demand for physiologically relevant and high-throughput screening platforms also increases. In recent years, 3D in vitro models have gained attention for their use in screening novel anticancer drugs. However, there are limited 3D in vitro models tested with chemotherapy agents specifically targeting endometrial cancer. Many current treatments have faltered due to the absence of predictive biomarkers or models that inaccurately represent the diseases and the tumor microenvironment. This discrepancy has resulted in variations among patients in response to treatment and eventual cancer recurrence. There is a pressing need to find a better way to screen for novel compounds or delivery systems.
Technology Description This technology is a three-dimensional (3D) in vitro multilayer hydrogel model that facilitates drug screening analysis. The 3D model incorporates human microvascular endothelial cells (hMVEC) and endometrial cancer cells (HEC-1A, Ishikawa, or KLE) atop hydrogel formulations mimicking cell-specific extracellular matrix components. This optimized 3D model adeptly captures variances in cell responses among endometrial cancer cell lines from distinct stages. The inventors employed the 3D model to compare cell viability, microvessel formation, and cancer invasion across Ishikawa, KLE, and HEC-1A cells after Paclitaxel exposure, delivered both as a free drug and loaded in poly(caprolactone) (PCL) nanoparticles.
Figure 1. (A) Schematic diagram of 3D endometrial cancer model (created with BioRender.com). 2D and 3D visualization of human microvascular endothelial cells (hMVEC) and endometrial cancer cells (HEC-1A). At time 0 hours (B and D) and 48 hours after seeded (C and D). 3D visualization created using FIJI (NIH). Endometrial cancer invasion 3D visualization was created from 22 z-stacks. Z-stack separation=85 µm. 3D surface plot, grid size:256, smoothing 3.5, z-scale 1.0. Images from the endometrial cancer cell line HEC-1A, endothelial cells and endometrial cancer cells were seeded in the optimized hydrogel formulation for 48 hours. Images were taken every 3 hours for 48 hours. Scale bar 1000 µm.
Figure 2. Engineering a specific multilayer multicellular model for endometrial cancer. Schematic of the DOE model designed with 45 unique hydrogel combinations.
Further Details:
Lab Website: https://sites.google.com/oregonstate.edu/fogglab/ Pre-print paper: https://www.biorxiv.org/content/10.1101/2024.02.20.581239v1
Features & Benefits
Applications
Opportunity Oregon State University is seeking a licensee to develop and fully validate endometrial cancer drug screening services that utilize the endometrial cancer model. Currently, both exclusive and non-exclusive licenses are available. They are also interested in working with industry partners under industry funded research agreements. Ideal industry collaborators will have compounds for screening or an interest in 3D model development. New ventures and startup opportunities are also under consideration.
Status Patent pending (U.S. provisional patent application)