Cargando…
Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin
Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396314/ https://www.ncbi.nlm.nih.gov/pubmed/34445591 http://dx.doi.org/10.3390/ijms22168887 |
_version_ | 1783744345242861568 |
---|---|
author | Kim, Jung Hoon Lee, Seungjin Kang, Su Jeong Choi, Young Wook Choi, Se Young Park, Joong Yull Chang, In Ho |
author_facet | Kim, Jung Hoon Lee, Seungjin Kang, Su Jeong Choi, Young Wook Choi, Se Young Park, Joong Yull Chang, In Ho |
author_sort | Kim, Jung Hoon |
collection | PubMed |
description | Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer. |
format | Online Article Text |
id | pubmed-8396314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83963142021-08-28 Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin Kim, Jung Hoon Lee, Seungjin Kang, Su Jeong Choi, Young Wook Choi, Se Young Park, Joong Yull Chang, In Ho Int J Mol Sci Article Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer. MDPI 2021-08-18 /pmc/articles/PMC8396314/ /pubmed/34445591 http://dx.doi.org/10.3390/ijms22168887 Text en © 2021 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 Kim, Jung Hoon Lee, Seungjin Kang, Su Jeong Choi, Young Wook Choi, Se Young Park, Joong Yull Chang, In Ho Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title | Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title_full | Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title_fullStr | Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title_full_unstemmed | Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title_short | Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin |
title_sort | establishment of three-dimensional bioprinted bladder cancer-on-a-chip with a microfluidic system using bacillus calmette–guérin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396314/ https://www.ncbi.nlm.nih.gov/pubmed/34445591 http://dx.doi.org/10.3390/ijms22168887 |
work_keys_str_mv | AT kimjunghoon establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT leeseungjin establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT kangsujeong establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT choiyoungwook establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT choiseyoung establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT parkjoongyull establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin AT changinho establishmentofthreedimensionalbioprintedbladdercanceronachipwithamicrofluidicsystemusingbacilluscalmetteguerin |