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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Jung Hoon, Lee, Seungjin, Kang, Su Jeong, Choi, Young Wook, Choi, Se Young, Park, Joong Yull, Chang, In Ho
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