Cell Rep Med. 2025 Feb 05. pii: S2666-3791(25)00011-4. [Epub ahead of print] 101938
Francesco Campo,
Alessia Neroni,
Cataldo Pignatelli,
Silvia Pellegrini,
Ilaria Marzinotto,
Libera Valla,
Fabio Manenti,
Martina Policardi,
Vito Lampasona,
Lorenzo Piemonti,
Antonio Citro.
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.
Keywords: beta cell replacement; extracellular matrix; human iPSC vascularized endocrine spheroids; iPSCs; induced pluripotent stem cells; islet transplantation; lung scaffold; organ decellularization; organ engineering for type 1 diabetes; pancreas bioengineering; tissue engineering; type 1 diabetes