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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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