ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions
Abstract Current in vitro models of 3D tumor spheroids within the microenvironment have emerged as promising tools for understanding tumor progression and potential drug responses. However, creating spheroids with functional vasculature remains challenging in a controlled and high‐throughput manner....
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202410659 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850272903225933824 |
|---|---|
| author | Jooyoung Ro Junyoung Kim Juhee Park Yongjun Choi Yoon‐Kyoung Cho |
| author_facet | Jooyoung Ro Junyoung Kim Juhee Park Yongjun Choi Yoon‐Kyoung Cho |
| author_sort | Jooyoung Ro |
| collection | DOAJ |
| description | Abstract Current in vitro models of 3D tumor spheroids within the microenvironment have emerged as promising tools for understanding tumor progression and potential drug responses. However, creating spheroids with functional vasculature remains challenging in a controlled and high‐throughput manner. Herein, a novel open 3D‐microarray platform is presented for a spheroid‐endothelium interaction (ODSEI) chip, capable of arraying more than 1000 spheroids on top of the vasculature, compartmentalized for single spheroid‐level analysis of drug resistance, and allows for the extraction of specific spheroids for further analysis. As proof of concept, the crosstalk between breast cancer spheroids and vasculature is monitored, validating the roles of endothelial cells in acquired tamoxifen resistance. Cancer spheroids exhibited reduced sensitivity to tamoxifen in the presence of vasculature. Further analysis through single‐cell RNA sequencing of extracted spheroids and protein arrays elucidated gene expression profiles and cytokines associated with acquired tamoxifen resistance, particularly involving the TNF‐α pathway via NF‐κB and mTOR signaling. By targeting the highly expressed cytokines (IL‐8, TIMP1) identified, tamoxifen resistance in cancer spheroid can be effectively reversed. In summary, the ODSEI chip allows to study spheroid and endothelial interaction in various contexts, leading to improved insights into tumor biology and therapeutic strategies. |
| format | Article |
| id | doaj-art-b3f4bffe70d24e11ae4423596edb1e13 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b3f4bffe70d24e11ae4423596edb1e132025-08-20T01:51:39ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202410659ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial InteractionsJooyoung Ro0Junyoung Kim1Juhee Park2Yongjun Choi3Yoon‐Kyoung Cho4Department of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 South KoreaDepartment of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 South KoreaCenter for Algorithmic and Robotized Synthesis Institute for Basic Science (IBS) Ulsan 44919 South KoreaCenter for Algorithmic and Robotized Synthesis Institute for Basic Science (IBS) Ulsan 44919 South KoreaDepartment of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 South KoreaAbstract Current in vitro models of 3D tumor spheroids within the microenvironment have emerged as promising tools for understanding tumor progression and potential drug responses. However, creating spheroids with functional vasculature remains challenging in a controlled and high‐throughput manner. Herein, a novel open 3D‐microarray platform is presented for a spheroid‐endothelium interaction (ODSEI) chip, capable of arraying more than 1000 spheroids on top of the vasculature, compartmentalized for single spheroid‐level analysis of drug resistance, and allows for the extraction of specific spheroids for further analysis. As proof of concept, the crosstalk between breast cancer spheroids and vasculature is monitored, validating the roles of endothelial cells in acquired tamoxifen resistance. Cancer spheroids exhibited reduced sensitivity to tamoxifen in the presence of vasculature. Further analysis through single‐cell RNA sequencing of extracted spheroids and protein arrays elucidated gene expression profiles and cytokines associated with acquired tamoxifen resistance, particularly involving the TNF‐α pathway via NF‐κB and mTOR signaling. By targeting the highly expressed cytokines (IL‐8, TIMP1) identified, tamoxifen resistance in cancer spheroid can be effectively reversed. In summary, the ODSEI chip allows to study spheroid and endothelial interaction in various contexts, leading to improved insights into tumor biology and therapeutic strategies.https://doi.org/10.1002/advs.202410659co‐culturedrug‐resistant mechanism studyopen microfluidicsspheroids |
| spellingShingle | Jooyoung Ro Junyoung Kim Juhee Park Yongjun Choi Yoon‐Kyoung Cho ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions Advanced Science co‐culture drug‐resistant mechanism study open microfluidics spheroids |
| title | ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions |
| title_full | ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions |
| title_fullStr | ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions |
| title_full_unstemmed | ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions |
| title_short | ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid‐Endothelial Interactions |
| title_sort | odsei chip an open 3d microfluidic platform for studying tumor spheroid endothelial interactions |
| topic | co‐culture drug‐resistant mechanism study open microfluidics spheroids |
| url | https://doi.org/10.1002/advs.202410659 |
| work_keys_str_mv | AT jooyoungro odseichipanopen3dmicrofluidicplatformforstudyingtumorspheroidendothelialinteractions AT junyoungkim odseichipanopen3dmicrofluidicplatformforstudyingtumorspheroidendothelialinteractions AT juheepark odseichipanopen3dmicrofluidicplatformforstudyingtumorspheroidendothelialinteractions AT yongjunchoi odseichipanopen3dmicrofluidicplatformforstudyingtumorspheroidendothelialinteractions AT yoonkyoungcho odseichipanopen3dmicrofluidicplatformforstudyingtumorspheroidendothelialinteractions |