Mooranian Armin, Ionescu Corina Mihaela, Wagle Susbin Raj, Kovacevic Bozica, Walker Daniel, Jones Melissa, Chester Jacqueline, Foster Thomas, Johnston Edan, Kojic Sanja, Stojanovic Goran, Mikov Momir, Al-Salami Hani
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia.
Pharmaceutics. 2021 Oct 16;13(10):1713. doi: 10.3390/pharmaceutics13101713.
Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic β-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D).
Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation.
Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-β, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.
多项研究表明，包含各种胆汁酸（如鹅去氧胆酸（CDCA））的不同生物材料和水凝胶，以及诸如聚（苯乙烯）磺酸盐（PSS）和聚（烯丙基）胺（PAA）等辅料，对封装的存活胰腺β细胞表现出积极的生物学效应。因此，本研究旨在探讨将CDCA与PSS和PAA结合是否会优化1型糖尿病（T1D）患者移植后封装胰岛的功能。
将小鼠制成T1D模型，分为两组，分别移植PSS - PAA（对照组）或CDCA - PSS - PAA（治疗组）微胶囊包裹的胰岛。移植后测量移植微胶囊对血糖、炎症和胆汁酸谱的影响。
与对照组相比，治疗组显示出更好的存活率、改善的血糖控制以及更低的炎症水平，表现为白细胞介素1 - β、白细胞介素 - 6、白细胞介素 - 12和肿瘤坏死因子 - α水平降低，以及血浆、肝脏、大肠和粪便中胆汁酸以及石胆酸水平降低。结果表明，将CDCA与PSS - PAA微胶囊结合对封装的胰岛产生了有益影响，并在移植后在局部和全身水平上增强了糖尿病治疗效果。
Zotero 插件
