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

AimTo evaluate the effect of pancreatic ductal cells on experimental human islet transplantation.Materials and methodsIsolated 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.ResultsInsulin stimulation index was higher in islets than in islets co-cultured with DPS (5.59 ± 0.93 vs 4.02 ± 0.46; pIL1B and CXCL11 expression was higher in 100 islets + 200 DPS than in islets (p0.05), 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; pIL1B and IL1RN expression was significantly higher in islets + DPS grafts.ConclusionsIslet 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.研究目的：评估胰腺导管细胞对实验性人胰岛移植的影响。 材料与方法：分离得到的人胰岛通过手工挑选进行进一步纯化。导管细胞经磁珠分选纯化后，聚集成胰腺导管球状体（ductal pancreatospheres, DPS）。将胰岛、DPS以及胰岛+DPS（100个胰岛+75个DPS，或100个胰岛+200个DPS）进行体外培养，检测葡萄糖刺激胰岛素分泌、β细胞凋亡以及基因表达情况。将胰岛及胰岛+DPS制剂（800个胰岛+600个DPS）移植至链脲佐菌素（streptozotocin）处理的免疫缺陷小鼠（immunodeficient mice）体内，检测血糖水平、移植物形态计量学指标及基因表达情况。 结果：单纯胰岛组的胰岛素刺激指数高于与DPS共培养的胰岛组（5.59±0.93 vs 4.02±0.46；P<0.05）。100个胰岛+200个DPS组的IL1B及CXCL11基因表达水平高于单纯胰岛组（P<0.05）；胰岛+DPS移植物的β细胞/内分泌非β细胞质量比更低（单纯胰岛组：2.05±0.18，胰岛+DPS组：1.35±0.15；P<0.05），且该移植物中IL1B及IL1RN的基因表达水平显著升高。 结论：富含导管细胞的胰岛制剂在体外的胰岛素刺激指数更低，移植后的代谢结局更差。炎症反应可能介导了导管细胞对胰岛细胞的有害作用。