AUTHOR=Honarpisheh M. , Lei Y. , Zhang Y. , Pehl M. , Kemter E. , Kraetzl M. , Lange A. , Wolf E. , Wolf-van Buerck L. , Seissler J. , the VANGUARD Consortium , Bellofatto Kevin , Berishvili Ekaterine , Bignard Juliette , Fonseca Laura Mar , Lebreton Fanny , Assanelli Simone , Borsotti Chiara , Cucci Alessia , Follenzi Antonia , Olgasi Cristina , Citro Antonio , Piemonti Lorenzo , Pellegrini Silvia , Thaunat Olivier , Jongh Dide de , Massey Emma , Bunnik Eline , Cronin Antonia J. , Mey Devi , Parisotto Chiara , Rossi Giovanna , Kugelmeier Patrick , Mühlemann Markus , Pal-Kutas Karolina , Wolint Petra , Cavallaro Marco , Götz Julia , Müller Jeanette TITLE=Formation of Re-Aggregated Neonatal Porcine Islet Clusters Improves In Vitro Function and Transplantation Outcome JOURNAL=Transplant International VOLUME=35 YEAR=2022 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10697 DOI=10.3389/ti.2022.10697 ISSN=1432-2277 ABSTRACT=

Neonatal porcine islet-like cell clusters (NPICCs) are a promising source for islet cell transplantation. Excellent islet quality is important to achieve a cure for type 1 diabetes. We investigated formation of cell clusters from dispersed NPICCs on microwell cell culture plates, evaluated the composition of re-aggregated porcine islets (REPIs) and compared in vivo function by transplantation into diabetic NOD‐SCID IL2rγ−/− (NSG) mice with native NPICCs. Dissociation of NPICCs into single cells and re-aggregation resulted in the formation of uniform REPI clusters. A higher prevalence of normoglycemia was observed in diabetic NSG mice after transplantation with a limited number (n = 1500) of REPIs (85.7%) versus NPICCs (n = 1500) (33.3%) (p < 0.05). Transplanted REPIs and NPICCs displayed a similar architecture of endocrine and endothelial cells. Intraperitoneal glucose tolerance tests revealed an improved beta cell function after transplantation of 1500 REPIs (AUC glucose 0–120 min 6260 ± 305.3) as compared to transplantation of 3000 native NPICCs (AUC glucose 0–120 min 8073 ± 536.2) (p < 0.01). Re-aggregation of single cells from dissociated NPICCs generates cell clusters with excellent functionality and improved in vivo function as compared to native NPICCs.