Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model
Purpose: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. Materials and Methods: We fabricated high-throughput BCOC with microfluidi...
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| Format: | Article |
| Language: | English |
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Korean Urological Association
2023-05-01
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| Series: | Investigative and Clinical Urology |
| Subjects: | |
| Online Access: | https://www.icurology.org/pdf/10.4111/icu.20220293 |
| _version_ | 1827950514966364160 |
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| author | Joongwon Choi Tae Young Jung Jung Hoon Kim Sejung Maeng Su Jeong Kang Mirinae Kim Young Wook Choi Se Young Choi Sung-Hwan Kim In Ho Chang |
| author_facet | Joongwon Choi Tae Young Jung Jung Hoon Kim Sejung Maeng Su Jeong Kang Mirinae Kim Young Wook Choi Se Young Choi Sung-Hwan Kim In Ho Chang |
| author_sort | Joongwon Choi |
| collection | DOAJ |
| description | Purpose: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model.
Materials and Methods: We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model.
Results: The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2±1.3, 10 MOI: 22.5±2.3, 1 MOI: 39.4±4.7, Mock: 54.9±10.8, control: 100.0±5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-α and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line.
Conclusions: In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment. |
| first_indexed | 2024-04-09T13:27:49Z |
| format | Article |
| id | doaj.art-c0f439a773de4d9abc3bdced76cc6360 |
| institution | Directory Open Access Journal |
| issn | 2466-0493 2466-054X |
| language | English |
| last_indexed | 2024-04-09T13:27:49Z |
| publishDate | 2023-05-01 |
| publisher | Korean Urological Association |
| record_format | Article |
| series | Investigative and Clinical Urology |
| spelling | doaj.art-c0f439a773de4d9abc3bdced76cc63602023-05-10T05:36:54ZengKorean Urological AssociationInvestigative and Clinical Urology2466-04932466-054X2023-05-0164329630510.4111/icu.20220293Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse modelJoongwon Choi 0https://orcid.org/0000-0001-5978-8179Tae Young Jung1https://orcid.org/0000-0002-4634-3370Jung Hoon Kim2https://orcid.org/0000-0002-0947-876XSejung Maeng 3https://orcid.org/0000-0002-0730-0300Su Jeong Kang4https://orcid.org/0000-0003-4324-8252Mirinae Kim5https://orcid.org/0000-0003-4199-8105Young Wook Choi6https://orcid.org/0000-0001-6659-3855Se Young Choi7https://orcid.org/0000-0002-4615-0966Sung-Hwan Kim8https://orcid.org/0000-0002-6868-4096In Ho Chang9https://orcid.org/0000-0003-0240-1310Department of Urology, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea.Department of Urology, VHS Medical Center, Seoul, Korea.Department of Urology, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Cellsmith Inc., Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Purpose: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. Materials and Methods: We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model. Results: The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2±1.3, 10 MOI: 22.5±2.3, 1 MOI: 39.4±4.7, Mock: 54.9±10.8, control: 100.0±5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-α and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line. Conclusions: In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment.https://www.icurology.org/pdf/10.4111/icu.20220293bioprintingmycobacterium bovistumor microenvironment |
| spellingShingle | Joongwon Choi Tae Young Jung Jung Hoon Kim Sejung Maeng Su Jeong Kang Mirinae Kim Young Wook Choi Se Young Choi Sung-Hwan Kim In Ho Chang Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model Investigative and Clinical Urology bioprinting mycobacterium bovis tumor microenvironment |
| title | Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model |
| title_full | Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model |
| title_fullStr | Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model |
| title_full_unstemmed | Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model |
| title_short | Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model |
| title_sort | efficacy of recombinant bacillus calmette guerin containing dlta in in vivo three dimensional bio printed bladder cancer on a chip and ex vivo orthotopic mouse model |
| topic | bioprinting mycobacterium bovis tumor microenvironment |
| url | https://www.icurology.org/pdf/10.4111/icu.20220293 |
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