Autoimmune β-cell loss in T1D occurs in a three-dimensional tissue context that current cell culture systems fail to replicate. HPSs preserve native islet-exocrine relationships and tissue architecture, providing a unique human platform to observe immune damage in real time. This revised application focuses on building controlled models of autoimmune β-cell injury, not on requesting rare disease-context tissue for initial model development. In collaboration with the Pastori, Agarwal, Abdulreda, Nakayama, Panzer, and Pugliese teams, we will combine non-diabetic HPSs with HLA-compatible autoreactive TCR transductants and cytokine conditioning in three complementary systems: standard slice culture, SliceChip/vascular SliceChip, and Slice-in-ACE. The goal is to establish interpretable platforms that distinguish antigen-specific β-cell injury from allogeneic or nonspecific tissue damage. Future use of T1D or AAb+ slices would be considered only through a later addendum or nPOD-approved rotation after completion of the go/no-go milestones described below.
