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A predictive computational platform for optimizing the design of bioartificial pancreas devices
The delivery of encapsulated islets or stem cell-derived insulin-producing cells (i.e., bioartificial pancreas devices) may achieve a functional cure for type 1 diabetes, but their efficacy is limited by mass transport constraints. Modeling such constraints is thus desirable, but previous efforts in...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561707/ https://www.ncbi.nlm.nih.gov/pubmed/36229614 http://dx.doi.org/10.1038/s41467-022-33760-5 |
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author | Ernst, Alexander U. Wang, Long-Hai Worland, Scott C. Marfil-Garza, Braulio A. Wang, Xi Liu, Wanjun Chiu, Alan Kin, Tatsuya O’Gorman, Doug Steinschneider, Scott Datta, Ashim K. Papas, Klearchos K. James Shapiro, A. M. Ma, Minglin |
author_facet | Ernst, Alexander U. Wang, Long-Hai Worland, Scott C. Marfil-Garza, Braulio A. Wang, Xi Liu, Wanjun Chiu, Alan Kin, Tatsuya O’Gorman, Doug Steinschneider, Scott Datta, Ashim K. Papas, Klearchos K. James Shapiro, A. M. Ma, Minglin |
author_sort | Ernst, Alexander U. |
collection | PubMed |
description | The delivery of encapsulated islets or stem cell-derived insulin-producing cells (i.e., bioartificial pancreas devices) may achieve a functional cure for type 1 diabetes, but their efficacy is limited by mass transport constraints. Modeling such constraints is thus desirable, but previous efforts invoke simplifications which limit the utility of their insights. Herein, we present a computational platform for investigating the therapeutic capacity of generic and user-programmable bioartificial pancreas devices, which accounts for highly influential stochastic properties including the size distribution and random localization of the cells. We first apply the platform in a study which finds that endogenous islet size distribution variance significantly influences device potency. Then we pursue optimizations, determining ideal device structures and estimates of the curative cell dose. Finally, we propose a new, device-specific islet equivalence conversion table, and develop a surrogate machine learning model, hosted on a web application, to rapidly produce these coefficients for user-defined devices. |
format | Online Article Text |
id | pubmed-9561707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95617072022-10-15 A predictive computational platform for optimizing the design of bioartificial pancreas devices Ernst, Alexander U. Wang, Long-Hai Worland, Scott C. Marfil-Garza, Braulio A. Wang, Xi Liu, Wanjun Chiu, Alan Kin, Tatsuya O’Gorman, Doug Steinschneider, Scott Datta, Ashim K. Papas, Klearchos K. James Shapiro, A. M. Ma, Minglin Nat Commun Article The delivery of encapsulated islets or stem cell-derived insulin-producing cells (i.e., bioartificial pancreas devices) may achieve a functional cure for type 1 diabetes, but their efficacy is limited by mass transport constraints. Modeling such constraints is thus desirable, but previous efforts invoke simplifications which limit the utility of their insights. Herein, we present a computational platform for investigating the therapeutic capacity of generic and user-programmable bioartificial pancreas devices, which accounts for highly influential stochastic properties including the size distribution and random localization of the cells. We first apply the platform in a study which finds that endogenous islet size distribution variance significantly influences device potency. Then we pursue optimizations, determining ideal device structures and estimates of the curative cell dose. Finally, we propose a new, device-specific islet equivalence conversion table, and develop a surrogate machine learning model, hosted on a web application, to rapidly produce these coefficients for user-defined devices. Nature Publishing Group UK 2022-10-13 /pmc/articles/PMC9561707/ /pubmed/36229614 http://dx.doi.org/10.1038/s41467-022-33760-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ernst, Alexander U. Wang, Long-Hai Worland, Scott C. Marfil-Garza, Braulio A. Wang, Xi Liu, Wanjun Chiu, Alan Kin, Tatsuya O’Gorman, Doug Steinschneider, Scott Datta, Ashim K. Papas, Klearchos K. James Shapiro, A. M. Ma, Minglin A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title | A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title_full | A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title_fullStr | A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title_full_unstemmed | A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title_short | A predictive computational platform for optimizing the design of bioartificial pancreas devices |
title_sort | predictive computational platform for optimizing the design of bioartificial pancreas devices |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561707/ https://www.ncbi.nlm.nih.gov/pubmed/36229614 http://dx.doi.org/10.1038/s41467-022-33760-5 |
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