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On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing
Organoid models have gained importance in recent years in determining the toxic effects of drugs in cancer studies. Organoid designs with the same standardized size and cellular structures are desired for drug tests. The field of microfluidics offers numerous advantages to enable well-controlled and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775535/ https://www.ncbi.nlm.nih.gov/pubmed/36551144 http://dx.doi.org/10.3390/bios12121177 |
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author | Ozcelik, Adem Abas, Burcin Irem Erdogan, Omer Cevik, Evrim Cevik, Ozge |
author_facet | Ozcelik, Adem Abas, Burcin Irem Erdogan, Omer Cevik, Evrim Cevik, Ozge |
author_sort | Ozcelik, Adem |
collection | PubMed |
description | Organoid models have gained importance in recent years in determining the toxic effects of drugs in cancer studies. Organoid designs with the same standardized size and cellular structures are desired for drug tests. The field of microfluidics offers numerous advantages to enable well-controlled and contamination-free biomedical research. In this study, simple and low-cost microfluidic devices were designed and fabricated to develop an organoid model for drug testing for renal cancers. Caki human renal cancer cells and mesenchymal stem cells isolated from human umbilical cord were placed into alginate hydrogels. The microfluidic system was implemented to form size-controllable organoids within alginate hydrogels. Alginate capsules of uniform sizes formed in the microfluidic system were kept in cell culture for 21 days, and their organoid development was studied with calcein staining. Cisplatin was used as a standard chemotherapeutic, and organoid sphere structures were examined as a function of time with an MTT assay. HIF-1α, CXCR4 and CXCL-12 chemokine protein, and CXCR4 and CXCL-12 gene levels were tested in organoids and cisplatin responses. In conclusion, it was found that the standard renal cancer organoids made on a lab-on-a-chip system can be used to measure drug effects and tumor microenvironment responses. |
format | Online Article Text |
id | pubmed-9775535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97755352022-12-23 On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing Ozcelik, Adem Abas, Burcin Irem Erdogan, Omer Cevik, Evrim Cevik, Ozge Biosensors (Basel) Article Organoid models have gained importance in recent years in determining the toxic effects of drugs in cancer studies. Organoid designs with the same standardized size and cellular structures are desired for drug tests. The field of microfluidics offers numerous advantages to enable well-controlled and contamination-free biomedical research. In this study, simple and low-cost microfluidic devices were designed and fabricated to develop an organoid model for drug testing for renal cancers. Caki human renal cancer cells and mesenchymal stem cells isolated from human umbilical cord were placed into alginate hydrogels. The microfluidic system was implemented to form size-controllable organoids within alginate hydrogels. Alginate capsules of uniform sizes formed in the microfluidic system were kept in cell culture for 21 days, and their organoid development was studied with calcein staining. Cisplatin was used as a standard chemotherapeutic, and organoid sphere structures were examined as a function of time with an MTT assay. HIF-1α, CXCR4 and CXCL-12 chemokine protein, and CXCR4 and CXCL-12 gene levels were tested in organoids and cisplatin responses. In conclusion, it was found that the standard renal cancer organoids made on a lab-on-a-chip system can be used to measure drug effects and tumor microenvironment responses. MDPI 2022-12-17 /pmc/articles/PMC9775535/ /pubmed/36551144 http://dx.doi.org/10.3390/bios12121177 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ozcelik, Adem Abas, Burcin Irem Erdogan, Omer Cevik, Evrim Cevik, Ozge On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title | On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title_full | On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title_fullStr | On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title_full_unstemmed | On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title_short | On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing |
title_sort | on-chip organoid formation to study cxcr4/cxcl-12 chemokine microenvironment responses for renal cancer drug testing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775535/ https://www.ncbi.nlm.nih.gov/pubmed/36551144 http://dx.doi.org/10.3390/bios12121177 |
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