Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes

Intrahepatic islet transplantation is the standard cell therapy for β cell replacement, but donor shortage and suboptimal engraftment limit its use in selected type 1 diabetes patients. There is an urgent need for strategies providing an unlimited source of insulin-producing cells and innovative scaffolds that foster cell interaction and integration to achieve physiological endocrine function. Building on prior work using decellularized lung as a scaffold for β cell replacement, this study integrates neonatal porcine islets (NPIs) with blood outgrowth endothelial cells (BOECs) derived from healthy subjects to engineer a xenogeneic vascularized endocrine pancreas (VEP). The authors validate ex vivo cell integration and function, and demonstrate engraftment and performance in a preclinical diabetes model. The VEP fosters NPI maturation in vitro and exhibits immediate in vivo function upon transplantation with sustained performance for over 18 weeks, exceeding the typical ~8-week timeline observed in state-of-the-art preclinical models. Given recent progress in donor pig genetic engineering, this technology may enable assembly of immune-protected functional endocrine organs.

Antonio Citro, Alessia Neroni, Cataldo Pignatelli, Francesco Campo, Martina Policardi, Matteo Monieri, Silvia Pellegrini, Erica Dugnani, Fabio Manenti, Maria Chiara Maffia, Libera Valla, Elisabeth Kemter, Ilaria Marzinotto, Cristina Olgasi, Alessia Cucci, Antonia Follenzi, Vito Lampasona, Eckhard Wolf, Lorenzo Piemonti