Pancreatic ductal cells may have a negative effect on human islet transplantation.

• Main Authors: Sandra Marín-Cañas, Elisabet Estil Les, Laura Llado, Patricia San José, Montserrat Nacher, Noèlia Téllez, Eduard Montanya
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-01-01
• Series: PLoS ONE
• Online Access: https://doi.org/10.1371/journal.pone.0220064

<h4>Aim</h4>To evaluate the effect of pancreatic ductal cells on experimental human islet transplantation.<h4>Materials and methods</h4>Isolated islets were additionally purified by handpicking. Ductal cells were purified by magnetic cell sorting and then clustered into ductal pancreatospheres (DPS). Islets, DPS, and islets + DPS (100 islets + 75 DPS, or 100 islets + 200 DPS) were cultured and glucose-stimulated insulin secretion, β-cell apoptosis, and gene expression was determined. Islets and islets + DPS preparations (800 islets + 600 DPS) were transplanted to streptozotocin-treated immunodeficient mice and glycemia, graft morphometry, and gene expression were determined.<h4>Results</h4>Insulin stimulation index was higher in islets than in islets co-cultured with DPS (5.59 ± 0.93 vs 4.02 ± 0.46; p<0.05). IL1B and CXCL11 expression was higher in 100 islets + 200 DPS than in islets (p<0.01), and IL-1β was detected in supernatants collected from DPS and islets + DPS preparations, but not in islets. Hyperglycemia developed in 33% and 67% of mice transplanted with islets or with islets + DPS respectively. β-cell mass was 26% lower in islets + DPS than in islets grafts (p>0.05), and the ratio β-/endocrine non-β-cell mass was lower in islets + DPS grafts (islets: 2.05 ± 0.18, islets + DPS: 1.35 ± 0.15; p<0.01). IL1B and IL1RN expression was significantly higher in islets + DPS grafts.<h4>Conclusions</h4>Islet preparations enriched with ductal cells have a lower insulin stimulation index in vitro and achieved a worse metabolic outcome after transplantation. Inflammation may mediate the deleterious effects of ductal cells on islet cells.