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Pancreatic ductal cells may have a negative effect on human islet transplantation.
PLoS One 2019; 14(7):e0220064Plos

Abstract

AIM

To evaluate the effect of pancreatic ductal cells on experimental human islet transplantation.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Clinical Science, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.Liver Transplant Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Endocrine Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Endocrine Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Clinical Science, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Clinical Science, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. Endocrine Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31323061

Citation

Marín-Cañas, Sandra, et al. "Pancreatic Ductal Cells May Have a Negative Effect On Human Islet Transplantation." PloS One, vol. 14, no. 7, 2019, pp. e0220064.
Marín-Cañas S, Estil Les E, Llado L, et al. Pancreatic ductal cells may have a negative effect on human islet transplantation. PLoS ONE. 2019;14(7):e0220064.
Marín-Cañas, S., Estil Les, E., Llado, L., San José, P., Nacher, M., Téllez, N., & Montanya, E. (2019). Pancreatic ductal cells may have a negative effect on human islet transplantation. PloS One, 14(7), pp. e0220064. doi:10.1371/journal.pone.0220064.
Marín-Cañas S, et al. Pancreatic Ductal Cells May Have a Negative Effect On Human Islet Transplantation. PLoS ONE. 2019;14(7):e0220064. PubMed PMID: 31323061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pancreatic ductal cells may have a negative effect on human islet transplantation. AU - Marín-Cañas,Sandra, AU - Estil Les,Elisabet, AU - Llado,Laura, AU - San José,Patricia, AU - Nacher,Montserrat, AU - Téllez,Noèlia, AU - Montanya,Eduard, Y1 - 2019/07/19/ PY - 2019/02/13/received PY - 2019/07/07/accepted PY - 2019/7/20/entrez PY - 2019/7/20/pubmed PY - 2019/7/20/medline SP - e0220064 EP - e0220064 JF - PloS one JO - PLoS ONE VL - 14 IS - 7 N2 - AIM: To evaluate the effect of pancreatic ductal cells on experimental human islet transplantation. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31323061/Pancreatic_ductal_cells_may_have_a_negative_effect_on_human_islet_transplantation L2 - http://dx.plos.org/10.1371/journal.pone.0220064 DB - PRIME DP - Unbound Medicine ER -