Borges Silva Isaura Beatriz, Borghuis Theo, Qin Tian, Sogayar Mari Cleide, de Vos Paul
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Cell and Molecular Therapy NUCEL Group, School of Medicine, University of São Paulo, São Paulo, Brazil.
Mater Today Bio. 2025 May 1;32:101812. doi: 10.1016/j.mtbio.2025.101812. eCollection 2025 Jun.
Encapsulation of human pancreatic islets in semipermeable membranes offers a promising, less invasive alternative to whole pancreas transplantation for Type 1 Diabetes (T1D), potentially reducing the need for immunosuppressive drugs and improving graft survival. However, the inflammatory environment during transplantation poses significant challenges, often leading to substantial graft loss. This study explores modifying the intracapsular environment with extracellular matrix (ECM) molecules - chondroitin sulfate (ChS), laminin (LN), and polymerized laminin (pLN) - to enhance islet cell resilience against cytokine-induced stress, associated with the post-transplantation environment. Encapsulated mouse insulinoma β-cells (MIN6) and human islets were exposed to pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α) over 1, 3, and 5 days. The results showed that LN and pLN in combination with ChS particularly improved outcomes, with LN reducing oxidative stress and pLN significantly lowering cell death and pro-inflammatory chemokine MCP-1 production. These findings highlight the potential of ECM-modified encapsulation to enhance the survival of transplanted islets, offering a more favorable approach for T1D treatment and allowing transplantation of pancreatic islets with fewer islets.
将人胰岛封装在半透膜中，为1型糖尿病（T1D）患者提供了一种有前景、侵入性较小的全胰腺移植替代方案，可能减少免疫抑制药物的使用并提高移植物存活率。然而，移植过程中的炎症环境带来了重大挑战，常常导致大量移植物丢失。本研究探索用细胞外基质（ECM）分子——硫酸软骨素（ChS）、层粘连蛋白（LN）和聚合层粘连蛋白（pLN）——来改变囊内环境，以增强胰岛细胞对与移植后环境相关的细胞因子诱导应激的抵抗力。将封装的小鼠胰岛素瘤β细胞（MIN6）和人胰岛暴露于促炎细胞因子（IL-1β、IFN-γ、TNF-α）中1天、3天和5天。结果表明，LN和pLN与ChS联合使用尤其能改善结果，其中LN可降低氧化应激，pLN能显著降低细胞死亡和促炎趋化因子MCP-1的产生。这些发现凸显了ECM修饰封装在提高移植胰岛存活率方面的潜力，为T1D治疗提供了一种更有利的方法，并允许使用更少的胰岛进行胰腺胰岛移植。
