Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication
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To address the gap between in vivo microenvironments and in vitro systems, we have developed a novel microfluidic device that precisely controls the spatial and temporal interactions between adjacent three-dimensional cellular environments.
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Endothelial cells, fibroblasts, and immune cells are the three main non-neoplastic cell types appearing in most cancers.
“Endothelial cells, fibroblasts, and immune cells are the three main cell types which appear in most cancers and are vital components in enhancing the drug resistance of tumors [103, 114-120].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [116]
The Introduction (page unavailable) identifies fibroblasts and infiltrating immune cells as surrounding non-tumor cells involved in tumor progression. The paper also studies endothelial cells and fibroblasts, but it does not say these three are the main non-neoplastic cell types in most cancers or establish the citing sentence’s drug-resistance claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAlmost all current microfluidic devices incorporating fluid flow can generate a shear stress with physiologically relevant value and can demonstrate the impact of shear stress in cultured tumor cells in vitro.
“Almost all current microfluidic devices incorporating fluid flow can generate a shear stress with physiologically relevant value and can demonstrate the impact of shear stress in cultured tumor cells in vitro [157-160].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [157]
The Introduction (page not available) says interstitial flow can exert shear stress and influence cell behavior, and the Discussion describes a microfluidic device that controls interstitial flow. But the paper does not establish that almost all flow-based microfluidic devices generate physiologically relevant shear stress. Its demonstrated application was vascular network formation using endothelial and stromal cells, not the effect of shear stress on cultured tumor cells. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThese three cell types are vital components in enhancing the drug resistance of tumors.
“Endothelial cells, fibroblasts, and immune cells are the three main cell types which appear in most cancers and are vital components in enhancing the drug resistance of tumors [103, 114-120].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [116]
The Introduction links fibroblasts and infiltrating immune cells to tumor progression, and the Discussion describes endothelial-cell vessel formation. Neither passage addresses whether these three cell types enhance tumor drug resistance; searches for drug resistance and treatment found no such passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMost research is focused on how IFP prompts cancer cell migration and metastasis.
“Most research is focused on how IFP prompts cancer cells migration and metastasis [157,[167][168][169].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [157]
The Introduction says interstitial flow can affect cellular behavior and that tumor progression depends on interactions with surrounding cells. It does not say that most research focuses on IFP-induced cancer-cell migration or metastasis. Searches for those topics found no passage making that claim. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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Cites
Cancer Metastasis: Building a Framework
Gupta, G. P., & Massagué, J. (2006) · Cell · doi:10.1016/j.cell.2006.11.001 · Cited by 4,230 · see citing works
Microenvironmental regulation of metastasis
Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684 · see citing works
The third dimension bridges the gap between cell culture and live tissue
Pampaloni, F., Reynaud, E. G., & Stelzer, E. H. K. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2236 · Cited by 2,817 · see citing works
THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES
BOYDEN, S. V. (1962) · The Journal of Experimental Medicine · doi:10.1084/jem.115.3.453 · Cited by 2,732 · see citing works
Bissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180 · see citing works
Modeling Tissue Morphogenesis and Cancer in 3D
Yamada, K. M., & Cukierman, E. (2007) · Cell · doi:10.1016/j.cell.2007.08.006 · Cited by 1,751 · see citing works
Molecular characterization of the tumor microenvironment in breast cancer
Allinen, M., Beroukhim, R., Cai, L., Brennan, C., Lahti-Domenici, J., Huang, H., Porter, D., Hu, M., Chin, L., Richardson, A., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.010 · Cited by 1,299 · see citing works
A Computational Tool for Quantitative Analysis of Vascular Networks
Zudaire, E., Gambardella, L., Kurcz, C., & Vermeren, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027385 · Cited by 1,074 · see citing works
TUMOR STROMA AND REGULATION OF CANCER DEVELOPMENT
Tlsty, T. D., & Coussens, L. M. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100224 · Cited by 981 · see citing works
High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array
Tung, Y.-C., Hsiao, A. Y., Allen, S. G., Torisawa, Y.-S., Ho, M., & Takayama, S. (2011) · The Analyst · doi:10.1039/c0an00609b · Cited by 969 · see citing works
Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors.
Zigmond, S. H. (1977) · The Journal of Cell Biology · doi:10.1083/jcb.75.2.606 · Cited by 913 · see citing works
Interstitial Flow and Its Effects in Soft Tissues
Swartz, M. A., & Fleury, M. E. (2007) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.9.060906.151850 · Cited by 589 · see citing works
Shields, J. D., Fleury, M. E., Yong, C., Tomei, A. A., Randolph, G. J., & Swartz, M. A. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.020 · Cited by 555 · see citing works
The role of pericytes in angiogenesis
Ribatti, D., Nico, B., & Enrico Crivellato, B. (2011) · The International Journal of Developmental Biology · doi:10.1387/ijdb.103167dr · Cited by 441 · see citing works
Micromechanical control of cell–cell interactions
Hui, E. E., & Bhatia, S. N. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608660104 · Cited by 392 · see citing works
<i>In Vitro</i> Perfused Human Capillary Networks
Moya, M. L., Hsu, Y.-H., Lee, A. P., Hughes, C. C. W., & George, S. C. (2013) · Tissue Engineering Part C: Methods · doi:10.1089/ten.tec.2012.0430 · Cited by 387 · see citing works
Self-citationSchwarz, U. S., & Gardel, M. L. (2012) · Journal of Cell Science · doi:10.1242/jcs.093716 · Cited by 340 · see citing works
Weigelt, B., Lo, A. T., Park, C. C., Gray, J. W., & Bissell, M. J. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0502-2 · Cited by 336 · see citing works
Chen, X., Aledia, A. S., Ghajar, C. M., Griffith, C. K., Putnam, A. J., Hughes, C. C. W., & George, S. C. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0314 · Cited by 313 · see citing works
Self-citationMicrofabrication of Hepatocyte/Fibroblast Co-cultures: Role of Homotypic Cell Interactions
Bhatia, S. N., Balis, U. J., Yarmush, M. L., & Toner, M. (1998) · Biotechnology Progress · doi:10.1021/bp980036j · Cited by 304 · see citing works
How the capillary burst microvalve works
Cho, H., Kim, H., Kang, J. Y., & Kim, T. S. (2006) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2006.10.077 · Cited by 298 · see citing works
Helm, C. E., Fleury, M. E., Zisch, A. H., Boschetti, F., & Swartz, M. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503681102 · Cited by 269 · see citing works
Kragstrup, T. W., Kjær, M., & Mackey, A. L. (2011) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2011.01377.x · Cited by 241 · see citing works
Role of the pericyte in wound healing
Crocker, D. J., Murad, T. M., & Geer, J. C. (1970) · Experimental and Molecular Pathology · doi:10.1016/0014-4800(70)90084-5 · Cited by 218 · see citing works
Ng, C. P., Helm, C. E., & Swartz, M. A. (2004) · Microvascular Research · doi:10.1016/j.mvr.2004.08.002 · Cited by 206 · see citing works
Chen, X., Aledia, A. S., Popson, S. A., Him, L., Hughes, C. C. W., & George, S. C. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0491 · Cited by 204 · see citing works
Self-citationKhademhosseini, A., Ferreira, L., Blumling, J., Yeh, J., Karp, J. M., Fukuda, J., & Langer, R. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.06.035 · Cited by 202 · see citing works
Hsu, Y., Moya, M. L., Hughes, C. C. W., George, S. C., & Lee, A. P. (2013) · Lab on a Chip · doi:10.1039/c3lc50424g · Cited by 192 · see citing works
Self-citationPericyte Dynamics during Angiogenesis: New Insights from New Identities
Stapor, P. C., Sweat, R. S., Dashti, D. C., Betancourt, A. M., & Murfee, W. L. (2014) · Journal of Vascular Research · doi:10.1159/000362276 · Cited by 186 · see citing works
Migration dynamics of breast cancer cells in a tunable 3D interstitial flow chamber
Haessler, U., Teo, J. C. M., Foretay, D., Renaud, P., & Swartz, M. A. (2012) · Integrative Biology · doi:10.1039/c1ib00128k · Cited by 176 · see citing works
Helm, C. E., Zisch, A. H., & Swartz, M. A. (2006) · Biotechnology and Bioengineering · doi:10.1002/bit.21185 · Cited by 143 · see citing works
Full range physiological mass transport control in 3D tissue cultures
Hsu, Y., Moya, M. L., Abiri, P., Hughes, C. C. W., George, S. C., & Lee, A. P. (2012) · Lab on a Chip · doi:10.1039/c2lc40787f · Cited by 125 · see citing works
Self-citationMicroscale Control of Cell Contact and Spacing via Three-Component Surface Patterning
Hui, E. E., & Bhatia, S. N. (2007) · Langmuir · doi:10.1021/la0630559 · Cited by 65 · see citing works
Bonvin, C., Overney, J., Shieh, A. C., Dixon, J. B., & Swartz, M. A. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22608 · Cited by 62 · see citing works
Jain, R. K., Stock, R. J., Chary, S. R., et al. (1990) · Microvascular Research · doi:10.1016/0026-2862(90)90060-5 · Cited by 48 · see citing works
Chen, G., Lv, Y., Guo, P., et al. (2013) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x11308040007 · Cited by 44 · see citing works
New radiopaque polyHEMA‐based hydrogel particles
Horák, D., Metalová, M., & Rypáček, F. (1997) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(199702)34:2 · Cited by 43 · see citing works
Takakura, N. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04275.x · Cited by 19 · see citing works
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Quintard, C., Tubbs, E., Jonsson, G., Jiao, J., Wang, J., Werschler, N., Laporte, C., Pitaval, A., Bah, T.-S., Pomeranz, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45710-4 · Cited by 387 · see citing works
Shirure, V. S., Bi, Y., Curtis, M. B., Lezia, A., Goedegebuure, M. M., Goedegebuure, S. P., Aft, R., Fields, R. C., & George, S. C. (2018) · Lab on a Chip · doi:10.1039/c8lc00596f · Cited by 316 · see citing works
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Nashimoto, Y., Hayashi, T., Kunita, I., Nakamasu, A., Torisawa, Y.-S., Nakayama, M., Takigawa-Imamura, H., Kotera, H., Nishiyama, K., Miura, T., et al. (2017) · Integrative Biology · doi:10.1039/c7ib00024c · Cited by 266 · see citing works
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Passier, R., Orlova, V., & Mummery, C. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.02.011 · Cited by 142 · see citing works
Alimperti, S., Mirabella, T., Bajaj, V., Polacheck, W., Pirone, D. M., Duffield, J., Eyckmans, J., Assoian, R. K., & Chen, C. S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618333114 · Cited by 122 · see citing works
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- Authors
- Alonzo, L. F., Moya, M. L., Shirure, V. S., & George, S. C.
- Affiliations
- University of California, Irvine (US)
- Washington University in St. Louis (US)
- Corresponding author
- George, Steven C.
- Venue
- Lab on a Chip
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2015
- Volume
- 15
- Issue
- 17
- Pages
- 3521-3529
- ISSN
- 1473-0189 (ISSN-L)
- 1473-0197
- PMC
- PMC4855298
- OpenAlex
- W1889480789
- Semantic Scholar
- 01091faa51db0886fb73842fbcb1e528f0ceebdc
- Cited by
- 66
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 12 · 2016: 5 · 2015: 3
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Lab on a Chip (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (F31 CA163049, F32 HL105055, R01 CA170879, UH3 TR00048)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- microfluidics, interstitial fluid flow, hydrostatic pressure, 3D cell culture, stromal cells, vasculogenesis, endothelial colony-forming cells, lung fibroblasts, soluble factors, vascular network formation, tissue engineering
- MeSH terms
- Cell Communication, Cells, Cultured, Equipment Design, Fibroblasts, Humans, Models, Biological, Cell Culture Techniques, Tissue Engineering, Extracellular Fluid, Microfluidic Analytical Techniques, Cellular Microenvironment
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