Bioprinted Patient‐Derived Organoid Arrays Capture Intrinsic and Extrinsic Tumor Features for Advanced Personalized Medicine
Heterogeneity and the absence of a tumor microenvironment (TME) in traditional patient-derived organoid (PDO) cultures limit their effectiveness for clinical use. Here, Embedded Bioprinting-enabled Arrayed PDOs (Eba-PDOs) featuring uniformly arrayed colorectal cancer (CRC) PDOs within a recreated TME is presented. This model faithfully reproduces critical TME attributes, including elevated matrix stiffness (≈7.5 kPa) and hypoxic conditions found in CRC. Transcriptomic and immunofluorescence microscopy analysis reveal that Eba-PDOs more accurately represent actual tissues compared to traditional PDOs. Furthermore, Eba-PDO effectively capture the variability of CEACAM5 expression-a critical CRC marker-across different patients, correlating with patient classification and differential responses to 5-fluorouracil treatment. This method achieves an uniform size and shape within PDOs from the same patient while preserving distinct morphological features among those from different individuals. These features of Eba-PDO enable the efficient development of a label-free, morphology-based predictive model using supervised learning, enhancing its suitability for clinical applications. Thus, this approach to PDO bioprinting is a promising tool for generating personalized tumor models and advancing precision medicine.
Authors
- Hye‐Jin Jeong (ORCID: https://orcid.org/0009-0004-7458-654X)
- In Ho Song (ORCID: https://orcid.org/0000-0001-6330-3453)
- Kyemyung Park (ORCID: https://orcid.org/0000-0002-4728-5387)
- Jin‐Hyung Shim (ORCID: https://orcid.org/0000-0002-5407-9020)
- Tae‐Eun Park (ORCID: https://orcid.org/0000-0003-3979-5405)
- Jung In Park (ORCID: https://orcid.org/0000-0002-4064-3022)
- Kyungjae Myung (ORCID: https://orcid.org/0000-0001-7975-6190)
- Hyeonseo Kim (ORCID: https://orcid.org/0000-0002-9802-1031)
- Samuel Sánchez (ORCID: https://orcid.org/0000-0001-9713-9997)
- Hyun‐Wook Kang (ORCID: https://orcid.org/0000-0001-5335-5604)
- Taejoon Kwon (ORCID: https://orcid.org/0000-0002-9794-6112)
- Jonghyeuk Han
- Chang Sik Yu (ORCID: https://orcid.org/0000-0001-9401-9981)
- Junyoung Choi (ORCID: https://orcid.org/0000-0002-4255-4402)
- Deok‐Beom Jung (ORCID: https://orcid.org/0000-0003-4314-6643)
- Seung‐Jae Myung (ORCID: https://orcid.org/0000-0003-0585-4016)
Institutions
- Ulsan College (KR)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Georgia Institute of Technology (US)
- Asan Medical Center (KR)
- The Wallace H. Coulter Department of Biomedical Engineering (US)
- University of Ulsan (KR)
- STR Biotech (South Korea) (KR)
- Institute for Basic Science (KR)
- Barcelona Institute of Science and Technology (ES)
- Bio-Medical Science (South Korea) (KR)
- Institute for Bioengineering of Catalonia (ES)
- Ulsan National Institute of Science and Technology (KR)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1002/advs.202407871
- Citations
- 13
- Primary Topic
- 3D Printing in Biomedical Research
- Type
- article
- Field-Weighted Citation Impact
- 8.76
Funders
- University of Ulsan