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A predictive computational platform for optimizing the design of bioartificial pancreas devices.

Authors :
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
Source :
Nature Communications; 10/13/2022, Vol. 13 Issue 1, p1-18, 18p
Publication Year :
2022

Abstract

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. Transplanting encapsulated insulin-producing cells may achieve a functional cure for type 1 diabetes, but efficacy is constrained by mass transfer limits. Here, the authors report a dynamic computational platform to investigate the therapeutic potency of such programmable bioartificial pancreas devices. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
13
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
159661939
Full Text :
https://doi.org/10.1038/s41467-022-33760-5