Polymerized laminin-modified microcapsules improve pancreatic islet resilience towards cytokine induced inflammatory stress and lower chemoattractant cytokine secretion

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.