Type 1 diabetes is caused by the destruction of the beta cells of the pancreatic islets. Islet transplantation aims to restore endogenous insulin production but is limited by hypoxia, detachment of the extracellular matrix (ECM), and immune rejection. This thesis develops a 3D imaging protocol combining tissue clearing and immunofluorescence to study, under hypoxic conditions, the reorganization of the ECM after islet isolation, revealing morphological alterations that could be compensated by bioactive encapsulation using biomaterials and stem cells. The thesis also validates a semi-automated digital image analysis method, demonstrating in vivo that islets grafted in bioactive capsules induce a stronger immune response than those with simple encapsulation. This work emphasizes that holistic and multidisciplinary strategies are essential to develop effective and clinically applicable islet transplantation solutions for treating type 1 diabetes.
Ramirez Acosta, M. (2025). Chronicle of an Islet Death Foretold : innovative methodological approaches to understand the fate of pancreatic islets in transplantation. https://hdl.handle.net/2078.5/248968