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

A predictive computational platform for optimizing the design of bioartificial pancreas devices.
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DOI:
10.1038/s41467-022-33760-5
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发表时间:
2022-10-13
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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递送包封的胰岛或干细胞衍生的胰岛素产生细胞(即,生物人工胰腺装置)可以实现1型糖尿病的功能性治愈,但是它们的功效受到质量运输约束的限制。因此,建模这样的约束是可取的,但以前的努力调用的简化,限制了他们的见解的效用。在这里,我们提出了一个计算平台,用于调查通用和用户可编程的生物人工胰腺设备的治疗能力,它占高度影响力的随机属性,包括细胞的大小分布和随机定位。我们首先在一项研究中应用该平台,该研究发现内源性胰岛大小分布差异显著影响器械效力。然后,我们追求优化,确定理想的设备结构和治疗细胞剂量的估计。最后,我们提出了一个新的,特定于设备的胰岛等效转换表,并开发了一个代理机器学习模型,托管在Web应用程序上,快速产生这些系数的用户定义的设备。移植封装的胰岛素产生细胞可以实现1型糖尿病的功能性治愈,但疗效受到传质限制的限制。在这里,作者报告了一个动态计算平台来研究这种可编程生物人工胰腺装置的治疗效力。
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.
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