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

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 and Lorenzo Piemonti
Additional contact information
Antonio Citro: IRCCS San Raffaele Scientific Institute
Alessia Neroni: IRCCS San Raffaele Scientific Institute
Cataldo Pignatelli: IRCCS San Raffaele Scientific Institute
Francesco Campo: IRCCS San Raffaele Scientific Institute
Martina Policardi: IRCCS San Raffaele Scientific Institute
Matteo Monieri: IRCCS San Raffaele Scientific Institute
Silvia Pellegrini: IRCCS San Raffaele Scientific Institute
Erica Dugnani: IRCCS San Raffaele Scientific Institute
Fabio Manenti: IRCCS San Raffaele Scientific Institute
Maria Chiara Maffia: IRCCS San Raffaele Scientific Institute
Libera Valla: IRCCS San Raffaele Scientific Institute
Elisabeth Kemter: Gene Center and Department of Veterinary Sciences, LMU Munich
Ilaria Marzinotto: IRCCS San Raffaele Scientific Institute
Cristina Olgasi: University of Piemonte Orientale
Alessia Cucci: University of Piemonte Orientale
Antonia Follenzi: University of Piemonte Orientale
Vito Lampasona: IRCCS San Raffaele Scientific Institute
Eckhard Wolf: Gene Center and Department of Veterinary Sciences, LMU Munich
Lorenzo Piemonti: IRCCS San Raffaele Scientific Institute

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Intrahepatic islet transplantation is the standard cell therapy for β cell replacement. However, the shortage of organ donors and an unsatisfactory engraftment limit its application to a selected patients with type 1 diabetes. There is an urgent need to identify alternative strategies based on an unlimited source of insulin producing cells and innovative scaffolds to foster cell interaction and integration to orchestrate physiological endocrine function. We previously proposed the use of decellularized lung as a scaffold for β cell replacement with the final goal of engineering a vascularized endocrine organ. Here, we prototyped this technology with the integration of neonatal porcine islet and healthy subject-derived blood outgrowth endothelial cells to engineer a xenogeneic vascularized endocrine pancreas. We validated ex vivo cell integration and function, its engraftment and performance in a preclinical model of diabetes. Results showed that this technology not only is able to foster neonatal pig islet maturation in vitro, but also to perform in vivo immediately upon transplantation and for over 18 weeks, compared to normal performance within 8 weeks in various state of the art preclinical models. Given the recent progress in donor pig genetic engineering, this technology may enable the assembly of immune-protected functional endocrine organs.

Date: 2023
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DOI: 10.1038/s41467-023-36582-1

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