Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterised by poor survival rates and an increasing global incidence. Advances in the staging and categorization of pancreatic tumours, along with the discovery of functional mutations, have made precision treatments possible,...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Materials Today Bio |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424003235 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846123309016547328 |
|---|---|
| author | Karina Goluba Vadims Parfejevs Evita Rostoka Kaspars Jekabsons Ilze Blake Anastasija Neimane Annija Anete Ule Roberts Rimsa Reinis Vangravs Andrejs Pcolkins Una Riekstina |
| author_facet | Karina Goluba Vadims Parfejevs Evita Rostoka Kaspars Jekabsons Ilze Blake Anastasija Neimane Annija Anete Ule Roberts Rimsa Reinis Vangravs Andrejs Pcolkins Una Riekstina |
| author_sort | Karina Goluba |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterised by poor survival rates and an increasing global incidence. Advances in the staging and categorization of pancreatic tumours, along with the discovery of functional mutations, have made precision treatments possible, which may lead to better clinical results. To further improve customized treatment approaches, in vitro models that can be used for functional drug sensitivity testing and precisely mimic the disease at the organ level are required. In this study, we present a workflow for creating a personalized PDAC chip utilising primary tumour-derived human pancreatic organoids (hPOs) and Human Umbilical Vein Endothelial Cells (HUVECs) to simulate the vascular barrier and tumour interactions within a PDMS-free organ-on-a-chip system. The patient PDAC tissue, expanded as tumour hPOs, could be cultured as adherent cells on the chip for more than 50 days, allowing continuous monitoring of cell viability through outflows from tumour and endothelial channels. Our findings demonstrate a gradual increase in cell density and cell turnover in the pancreatic tumor channel. Tumour-specific biomarkers, including CA-19.9, TIMP-1, Osteopontin, MIC-1, ICAM-1 and sAXL were consistently detected in the PDAC chip outflows. Comparative analyses between tissue culture plates and microfluidic conditions revealed significant differences in biomarker secretion patterns, highlighting the advantages of the microfluidics approach. This PDAC chip provides a stable, reproducible tumour model system with a functional endothelial cell barrier, suitable for drug sensitivity and secretory biomarker studies, thus serving as a platform for functional precision medicine application and multi-organ chip development. |
| format | Article |
| id | doaj-art-01a161a3e4874815bb09c01ca0e55f36 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-01a161a3e4874815bb09c01ca0e55f362024-12-14T06:32:02ZengElsevierMaterials Today Bio2590-00642024-12-0129101262Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applicationsKarina Goluba0Vadims Parfejevs1Evita Rostoka2Kaspars Jekabsons3Ilze Blake4Anastasija Neimane5Annija Anete Ule6Roberts Rimsa7Reinis Vangravs8Andrejs Pcolkins9Una Riekstina10Pharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, LatviaInstitute of Solid State Physics, University of Latvia, Kengaraga iela 8, Riga, LatviaInstitute of Solid State Physics, University of Latvia, Kengaraga iela 8, Riga, LatviaLatvian Centre of Infectious Diseases, Laboratory Service, Riga East University Hospital, Linezera iela 3, LV-1006, Riga, LatviaDepartment of Abdominal and Soft Tissue Surgery, Riga East Clinical University Hospital, Hipokrata iela 2, Riga, LatviaPharmaceutical Sciences Center, Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, Riga, Latvia; Corresponding author.Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterised by poor survival rates and an increasing global incidence. Advances in the staging and categorization of pancreatic tumours, along with the discovery of functional mutations, have made precision treatments possible, which may lead to better clinical results. To further improve customized treatment approaches, in vitro models that can be used for functional drug sensitivity testing and precisely mimic the disease at the organ level are required. In this study, we present a workflow for creating a personalized PDAC chip utilising primary tumour-derived human pancreatic organoids (hPOs) and Human Umbilical Vein Endothelial Cells (HUVECs) to simulate the vascular barrier and tumour interactions within a PDMS-free organ-on-a-chip system. The patient PDAC tissue, expanded as tumour hPOs, could be cultured as adherent cells on the chip for more than 50 days, allowing continuous monitoring of cell viability through outflows from tumour and endothelial channels. Our findings demonstrate a gradual increase in cell density and cell turnover in the pancreatic tumor channel. Tumour-specific biomarkers, including CA-19.9, TIMP-1, Osteopontin, MIC-1, ICAM-1 and sAXL were consistently detected in the PDAC chip outflows. Comparative analyses between tissue culture plates and microfluidic conditions revealed significant differences in biomarker secretion patterns, highlighting the advantages of the microfluidics approach. This PDAC chip provides a stable, reproducible tumour model system with a functional endothelial cell barrier, suitable for drug sensitivity and secretory biomarker studies, thus serving as a platform for functional precision medicine application and multi-organ chip development.http://www.sciencedirect.com/science/article/pii/S2590006424003235 |
| spellingShingle | Karina Goluba Vadims Parfejevs Evita Rostoka Kaspars Jekabsons Ilze Blake Anastasija Neimane Annija Anete Ule Roberts Rimsa Reinis Vangravs Andrejs Pcolkins Una Riekstina Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications Materials Today Bio |
| title | Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications |
| title_full | Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications |
| title_fullStr | Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications |
| title_full_unstemmed | Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications |
| title_short | Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications |
| title_sort | personalized pdac chip with functional endothelial barrier for tumour biomarker detection a platform for precision medicine applications |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424003235 |
| work_keys_str_mv | AT karinagoluba personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT vadimsparfejevs personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT evitarostoka personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT kasparsjekabsons personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT ilzeblake personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT anastasijaneimane personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT annijaaneteule personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT robertsrimsa personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT reinisvangravs personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT andrejspcolkins personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications AT unariekstina personalizedpdacchipwithfunctionalendothelialbarrierfortumourbiomarkerdetectionaplatformforprecisionmedicineapplications |