Journal Article Ppublish 1 citation
PubMed: 39922198 DOI: 10.1016/j.xcrm.2025.101938
Bioengineering of a human iPSC-derived vascularized endocrine pancreas for type 1 diabetes.
Cell Rep Med 6(2):101938
Authors: Francesco Campo, Alessia Neroni, Cataldo Pignatelli, Silvia Pellegrini, Ilaria Marzinotto, Libera Valla, Fabio Manenti, Martina Policardi, Vito Lampasona, Lorenzo Piemonti, Antonio Citro
Affiliations
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy.
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany.
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Abstract
Intrahepatic islet transplantation in patients with type 1 diabetes is limited by donor availability and lack of engraftment. Alternative β cell sources and transplantation sites are needed. We demonstrate the feasibility to repurpose a decellularized lung as an endocrine pancreas for β cell replacement. We bioengineer an induced pluripotent stem cell (iPSC)-based version, fabricating a human iPSC-based vascularized endocrine pancreas (iVEP) using iPSC-derived β cells (iPSC-derived islets [SC-islets]) and endothelial cells (iECs). SC-islets and iECs are aggregated into vascularized iβ spheroids (ViβeSs), and over 7 days of culture, spheroids integrate into the bioengineered vasculature, generating a functional, perfusable human endocrine organ. In vitro, the vascularized extracellular matrix (ECM) sustained SC-islet engraftment and survival with a significantly preserved β cell mass and a physiologic insulin release. In vivo, iVEP restores normoglycemia in diabetic NSG mice. We report a human iVEP providing a controlled in vitro insulin-secreting phenotype and in vivo function.
MeSH
Diabetes Mellitus, Cells, Islets Of Langerhans, Bioengineering, Insulin, Biological Science Disciplines, Islets Of Langerhans Transplantation, Pancreas, Induced Pluripotent Stem Cells, Tissue Engineering, Extracellular Matrix, Transplantation, Diabetes Mellitus, Type 1