Bioprinted Patient-Derived Organoid Arrays Capture Intrinsic and Extrinsic Tumor Features for Advanced Personalized...

Area of Science:

• Biotechnology
• Cancer Research
• Tissue Engineering

Background:

• Traditional patient-derived organoid (PDO) cultures lack tumor microenvironment (TME) components and exhibit heterogeneity, limiting their clinical utility.
• Colorectal cancer (CRC) is characterized by a complex TME, including matrix stiffness and hypoxia, which are crucial for tumor progression and treatment response.

Purpose of the Study:

• To develop a novel 3D bioprinting platform for creating arrayed PDOs within a recreated TME (Eba-PDOs).
• To assess the fidelity of Eba-PDOs in mimicking in vivo CRC conditions and patient-specific characteristics.
• To establish a predictive model for treatment response based on Eba-PDO morphology and supervised learning.

Main Methods:

• Embedded Bioprinting-enabled Arrayed PDOs (Eba-PDOs) were fabricated to incorporate CRC PDOs within a simulated TME.
• Eba-PDOs were characterized for matrix stiffness, hypoxia, transcriptomic profiles, and CEACAM5 expression.
• Immunofluorescence microscopy and supervised learning were employed to analyze morphology and predict treatment response.

Main Results:

• Eba-PDOs successfully replicated key TME attributes, including elevated matrix stiffness (≈7.5 kPa) and hypoxic conditions.
• Transcriptomic and immunofluorescence analyses showed Eba-PDOs more accurately represent native tissues than traditional PDOs.
• Eba-PDOs captured patient-specific CEACAM5 expression variability, correlating with patient classification and differential 5-fluorouracil response.

Conclusions:

• Eba-PDOs provide a more clinically relevant and accurate model for studying colorectal cancer.
• The developed morphology-based predictive model using Eba-PDOs enhances suitability for clinical applications.
• This bioprinting approach is a promising tool for generating personalized tumor models and advancing precision medicine in oncology.