TY - JOUR
T1 - A predictive computational platform for optimizing the design of bioartificial pancreas devices
AU - Ernst, Alexander U.
AU - Wang, Long Hai
AU - Worland, Scott C.
AU - Marfil-Garza, Braulio A.
AU - Wang, Xi
AU - Liu, Wanjun
AU - Chiu, Alan
AU - Kin, Tatsuya
AU - O’Gorman, Doug
AU - Steinschneider, Scott
AU - Datta, Ashim K.
AU - Papas, Klearchos K.
AU - James Shapiro, A. M.
AU - Ma, Minglin
N1 - Funding Information:
This work was partially supported by the National Institutes of Health (NIH, 1R01DK105967), the Novo Nordisk Company, the Juvenile Diabetes Research Foundation (JDRF, 2-SRA-2018-472-S-B), and the Hartwell Foundation (M.M.). This material is also based upon work supported by the National Science Foundation Graduate Research Fellowship under grant number DGE-1650441 (A.U.E.). Some schematics in Figs. 1a and 4a were created with BioRender.com. We thank the Cornell University Animal Health Diagnostic Center for histological sectioning and staining, the Alberta Diabetes Institute IsletCore at the University of Alberta for permitting the use of their human islet isolation data, and the Professor Millman group and Novo Nordisk for their generous provision of their respective stem cells and related information.
Funding Information:
This work was partially supported by the National Institutes of Health (NIH, 1R01DK105967), the Novo Nordisk Company, the Juvenile Diabetes Research Foundation (JDRF, 2-SRA-2018-472-S-B), and the Hartwell Foundation (M.M.). This material is also based upon work supported by the National Science Foundation Graduate Research Fellowship under grant number DGE-1650441 (A.U.E.). Some schematics in Figs. and were created with BioRender.com. We thank the Cornell University Animal Health Diagnostic Center for histological sectioning and staining, the Alberta Diabetes Institute IsletCore at the University of Alberta for permitting the use of their human islet isolation data, and the Professor Millman group and Novo Nordisk for their generous provision of their respective stem cells and related information.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-33760-5
DO - 10.1038/s41467-022-33760-5
M3 - Article
C2 - 36229614
AN - SCOPUS:85139938812
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6031
ER -