Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy
Abstract Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for p...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-02-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202303088 |
| _version_ | 1797329379632611328 |
|---|---|
| author | Daheui Choi Alan M. Gonzalez‐Suarez Mihai G. Dumbrava Michael Medlyn Jose M. deHoyos‐Vega Frank Cichocki Jeffrey S. Miller Li Ding Mojun Zhu Gulnaz Stybayeva Alexandre Gaspar‐Maia Daniel D. Billadeau Wen Wee Ma Alexander Revzin |
| author_facet | Daheui Choi Alan M. Gonzalez‐Suarez Mihai G. Dumbrava Michael Medlyn Jose M. deHoyos‐Vega Frank Cichocki Jeffrey S. Miller Li Ding Mojun Zhu Gulnaz Stybayeva Alexandre Gaspar‐Maia Daniel D. Billadeau Wen Wee Ma Alexander Revzin |
| author_sort | Daheui Choi |
| collection | DOAJ |
| description | Abstract Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments. |
| first_indexed | 2024-03-08T07:04:50Z |
| format | Article |
| id | doaj.art-8bace5ec4db746318ee3c8614e155c51 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T07:04:50Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-8bace5ec4db746318ee3c8614e155c512024-02-03T05:02:44ZengWileyAdvanced Science2198-38442024-02-01115n/an/a10.1002/advs.202303088Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and ImmunotherapyDaheui Choi0Alan M. Gonzalez‐Suarez1Mihai G. Dumbrava2Michael Medlyn3Jose M. deHoyos‐Vega4Frank Cichocki5Jeffrey S. Miller6Li Ding7Mojun Zhu8Gulnaz Stybayeva9Alexandre Gaspar‐Maia10Daniel D. Billadeau11Wen Wee Ma12Alexander Revzin13Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USADepartment of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USADivision of Experimental Pathology Mayo Clinic Rochester MN 55905 USADivision of Oncology Research College of Medicine Mayo Clinic Rochester MN 55905 USADepartment of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USADepartment of Medicine University of Minnesota Minneapolis MN 55455 USADepartment of Medicine University of Minnesota Minneapolis MN 55455 USADivision of Oncology Research College of Medicine Mayo Clinic Rochester MN 55905 USADivision of Medical Oncology Mayo Clinic Rochester MN 55905 USADepartment of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USADivision of Experimental Pathology Mayo Clinic Rochester MN 55905 USADivision of Oncology Research College of Medicine Mayo Clinic Rochester MN 55905 USADivision of Medical Oncology Mayo Clinic Rochester MN 55905 USADepartment of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USAAbstract Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.https://doi.org/10.1002/advs.202303088chemotherapyimmunotherapymicrofluidic devicepancreatic cancerpatient‐derived organoid |
| spellingShingle | Daheui Choi Alan M. Gonzalez‐Suarez Mihai G. Dumbrava Michael Medlyn Jose M. deHoyos‐Vega Frank Cichocki Jeffrey S. Miller Li Ding Mojun Zhu Gulnaz Stybayeva Alexandre Gaspar‐Maia Daniel D. Billadeau Wen Wee Ma Alexander Revzin Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy Advanced Science chemotherapy immunotherapy microfluidic device pancreatic cancer patient‐derived organoid |
| title | Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy |
| title_full | Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy |
| title_fullStr | Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy |
| title_full_unstemmed | Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy |
| title_short | Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy |
| title_sort | microfluidic organoid cultures derived from pancreatic cancer biopsies for personalized testing of chemotherapy and immunotherapy |
| topic | chemotherapy immunotherapy microfluidic device pancreatic cancer patient‐derived organoid |
| url | https://doi.org/10.1002/advs.202303088 |
| work_keys_str_mv | AT daheuichoi microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT alanmgonzalezsuarez microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT mihaigdumbrava microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT michaelmedlyn microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT josemdehoyosvega microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT frankcichocki microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT jeffreysmiller microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT liding microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT mojunzhu microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT gulnazstybayeva microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT alexandregasparmaia microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT danieldbilladeau microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT wenweema microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy AT alexanderrevzin microfluidicorganoidculturesderivedfrompancreaticcancerbiopsiesforpersonalizedtestingofchemotherapyandimmunotherapy |