Oniris, INRAE, IECM, USC 1383, 44300, Nantes, France.
SSR Pédiatriques ESEAN-APF France Handicap, Nantes University Hospital, Nantes, France.
Sci Rep. 2022 Mar 18;12(1):4681. doi: 10.1038/s41598-022-07887-w.
A bioartificial pancreas (BAP) encapsulating high pancreatic islets concentration is a promising alternative for type 1 diabetes therapy. However, the main limitation of this approach is O supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O-balanced BAP using statistical design of experiment (DoE). A full factorial DoE was first performed to screen two O-technologies on their ability to preserve pseudo-islet viability and function under hypoxia and normoxia. Then, response surface methodology was used to define the optimal O-carrier and islet seeding concentrations to maximize the number of viable pseudo-islets in the BAP containing an O-generator under hypoxia. Monitoring of viability, function and maturation of neonatal pig islets for 15 days in vitro demonstrated the efficiency of the optimal O-balanced BAP. The findings should allow the design of a more realistic BAP for humans with high islets concentration by maintaining the O balance in the device.
一种高胰岛浓度的生物人工胰腺（BAP）是 1 型糖尿病治疗的一种很有前途的替代方法。然而，这种方法的主要限制是 O 供应，特别是直到移植物新血管化。在这里，我们描述了一种使用实验设计（DoE）的统计学方法来设计最佳 O 平衡的 BAP。首先进行完全析因 DoE 以筛选两种 O 技术在低氧和常氧条件下保存假胰岛活力和功能的能力。然后，使用响应面法来确定最佳 O 载体和胰岛接种浓度，以在含有 O 发生器的 BAP 中最大限度地增加低氧条件下存活的假胰岛数量。体外监测新生猪胰岛 15 天的活力、功能和成熟度证明了最佳 O 平衡 BAP 的有效性。这些发现应该可以通过在设备中保持 O 平衡，设计出一种更适合高胰岛浓度的人类的更现实的 BAP。
