Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach
The development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a de...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/12/1962 |
| _version_ | 1797488943965405184 |
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| author | Lindsay R. Piraino Danielle S. W. Benoit Lisa A. DeLouise |
| author_facet | Lindsay R. Piraino Danielle S. W. Benoit Lisa A. DeLouise |
| author_sort | Lindsay R. Piraino |
| collection | DOAJ |
| description | The development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a design of experiments (DoE) approach to test combinations of seven soluble cues that were previously shown to maintain or improve salivary gland cell function. This approach uses statistical techniques to improve efficiency and accuracy of combinations of factors. The DoE-designed culture conditions improve markers of salivary gland function. Data show that the EGFR inhibitor, EKI-785, maintains relative mRNA expression of Mist1, a key acinar cell transcription factor, while FGF10 and neurturin promote mRNA expression of Aqp5 and Tmem16a, channel proteins involved in secretion. Mist1 mRNA expression correlates with increased secretory function, including calcium signaling and mucin (PAS-AB) staining. Overall, this study demonstrates that media conditions can be efficiently optimized to support secretory function in vitro using a DoE approach. |
| first_indexed | 2024-03-10T00:09:32Z |
| format | Article |
| id | doaj.art-cd78e068aff0403fbc6e01b19162a1cc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:09:32Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cd78e068aff0403fbc6e01b19162a1cc2023-11-23T16:02:16ZengMDPI AGCells2073-44092022-06-011112196210.3390/cells11121962Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) ApproachLindsay R. Piraino0Danielle S. W. Benoit1Lisa A. DeLouise2Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USADepartment of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USADepartment of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USAThe development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a design of experiments (DoE) approach to test combinations of seven soluble cues that were previously shown to maintain or improve salivary gland cell function. This approach uses statistical techniques to improve efficiency and accuracy of combinations of factors. The DoE-designed culture conditions improve markers of salivary gland function. Data show that the EGFR inhibitor, EKI-785, maintains relative mRNA expression of Mist1, a key acinar cell transcription factor, while FGF10 and neurturin promote mRNA expression of Aqp5 and Tmem16a, channel proteins involved in secretion. Mist1 mRNA expression correlates with increased secretory function, including calcium signaling and mucin (PAS-AB) staining. Overall, this study demonstrates that media conditions can be efficiently optimized to support secretory function in vitro using a DoE approach.https://www.mdpi.com/2073-4409/11/12/1962salivary glanddesign of experimentsMist1acinar cellEGFR inhibitor |
| spellingShingle | Lindsay R. Piraino Danielle S. W. Benoit Lisa A. DeLouise Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach Cells salivary gland design of experiments Mist1 acinar cell EGFR inhibitor |
| title | Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach |
| title_full | Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach |
| title_fullStr | Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach |
| title_full_unstemmed | Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach |
| title_short | Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach |
| title_sort | optimizing soluble cues for salivary gland tissue mimetics using a design of experiments doe approach |
| topic | salivary gland design of experiments Mist1 acinar cell EGFR inhibitor |
| url | https://www.mdpi.com/2073-4409/11/12/1962 |
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