A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions
Abstract Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cel...
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Nature Portfolio
2021
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oai:doaj.org-article:8cf0ffca17424706a726f4770e2e96bd2021-12-02T17:48:00ZA high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions10.1038/s41598-021-90833-z2045-2322https://doaj.org/article/8cf0ffca17424706a726f4770e2e96bd2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90833-zhttps://doaj.org/toc/2045-2322Abstract Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.Miles T. RogersAshley L. GardRobert GaiblerThomas J. MulhernRivka StrelnikovHesham AzizgolshaniBrian P. CainBrett C. IsenbergNerses J. HaroutunianNicole E. RaustadPhilip M. KeeganMatthew P. LechLindsay TomlinsonJeffrey T. BorensteinJoseph L. CharestCorin WilliamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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DOAJ |
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DOAJ |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Miles T. Rogers Ashley L. Gard Robert Gaibler Thomas J. Mulhern Rivka Strelnikov Hesham Azizgolshani Brian P. Cain Brett C. Isenberg Nerses J. Haroutunian Nicole E. Raustad Philip M. Keegan Matthew P. Lech Lindsay Tomlinson Jeffrey T. Borenstein Joseph L. Charest Corin Williams A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| description |
Abstract Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery. |
| format |
article |
| author |
Miles T. Rogers Ashley L. Gard Robert Gaibler Thomas J. Mulhern Rivka Strelnikov Hesham Azizgolshani Brian P. Cain Brett C. Isenberg Nerses J. Haroutunian Nicole E. Raustad Philip M. Keegan Matthew P. Lech Lindsay Tomlinson Jeffrey T. Borenstein Joseph L. Charest Corin Williams |
| author_facet |
Miles T. Rogers Ashley L. Gard Robert Gaibler Thomas J. Mulhern Rivka Strelnikov Hesham Azizgolshani Brian P. Cain Brett C. Isenberg Nerses J. Haroutunian Nicole E. Raustad Philip M. Keegan Matthew P. Lech Lindsay Tomlinson Jeffrey T. Borenstein Joseph L. Charest Corin Williams |
| author_sort |
Miles T. Rogers |
| title |
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| title_short |
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| title_full |
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| title_fullStr |
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| title_full_unstemmed |
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| title_sort |
high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/8cf0ffca17424706a726f4770e2e96bd |
| work_keys_str_mv |
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