Pancreatic ductal cells may have a negative effect on human islet transplantation.
<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 ducta...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0220064 |
| _version_ | 1830443645824663552 |
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| author | Sandra Marín-Cañas Elisabet Estil Les Laura Llado Patricia San José Montserrat Nacher Noèlia Téllez Eduard Montanya |
| author_facet | Sandra Marín-Cañas Elisabet Estil Les Laura Llado Patricia San José Montserrat Nacher Noèlia Téllez Eduard Montanya |
| author_sort | Sandra Marín-Cañas |
| collection | DOAJ |
| description | <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. |
| first_indexed | 2024-12-21T06:02:07Z |
| format | Article |
| id | doaj.art-34161ba5a9d946ccabd4c38e434bdddd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:02:07Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-34161ba5a9d946ccabd4c38e434bdddd2022-12-21T19:13:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e022006410.1371/journal.pone.0220064Pancreatic ductal cells may have a negative effect on human islet transplantation.Sandra Marín-CañasElisabet Estil LesLaura LladoPatricia San JoséMontserrat NacherNoèlia TéllezEduard Montanya<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.https://doi.org/10.1371/journal.pone.0220064 |
| spellingShingle | Sandra Marín-Cañas Elisabet Estil Les Laura Llado Patricia San José Montserrat Nacher Noèlia Téllez Eduard Montanya Pancreatic ductal cells may have a negative effect on human islet transplantation. PLoS ONE |
| title | Pancreatic ductal cells may have a negative effect on human islet transplantation. |
| title_full | Pancreatic ductal cells may have a negative effect on human islet transplantation. |
| title_fullStr | Pancreatic ductal cells may have a negative effect on human islet transplantation. |
| title_full_unstemmed | Pancreatic ductal cells may have a negative effect on human islet transplantation. |
| title_short | Pancreatic ductal cells may have a negative effect on human islet transplantation. |
| title_sort | pancreatic ductal cells may have a negative effect on human islet transplantation |
| url | https://doi.org/10.1371/journal.pone.0220064 |
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