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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85139938812&partnerID=8YFLogxK
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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
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6031
ER -