Stuart A Robertson1, Autumn M Rowan-Hull, Paul R V Johnson. 1. Paediatric Surgical Research Laboratory, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom.
Abstract
BACKGROUND/ PURPOSE: Islet transplantation offers the potential to reverse diabetes soon after diagnosis and has achieved considerable success in adults. Its use in children has been limited by long-term immunosuppression requirements and donor pancreas shortages. An ideal alternative source of islets would be from autologous precursor cells. The aim of this study was to determine whether the spleen can produce insulin-producing cells (IPCs) in our established model of pancreatic development. METHODS: Embryonic quail spleens (day 4.5) and chick pancreatic epithelium (day 4) were microdissected and recombined in a ratio of 1:1 (n = 12), 2:1 (n = 9) and 2:2 (n = 5). They were cultured for 7 days, sectioned, and analysed by fluorescent immunochemistry. Controls were performed to ensure clean separation. RESULTS: Overall, 12 (46%) of 26 recombinants contained IPCs of splenic origin, occurring in 5 (42%) of 12 of the of 1 spleen-1 epithelium recombinants, 3 (33%) of 9 of the 2 spleen-1 epithelium recombinants, and 4 (80%) of 5 of the 2 spleen-2 epithelia recombinants. Controls were negative. CONCLUSIONS: Preliminary results suggest developing avian spleens can differentiate into IPCs. Increased tissue mass enhanced the likelihood of this occurring. Mesenchyme-to-epithelia ratio did not influence this. The spleen could be an ideal autologous islet source for transplantation in children.
BACKGROUND/ PURPOSE: Islet transplantation offers the potential to reverse diabetes soon after diagnosis and has achieved considerable success in adults. Its use in children has been limited by long-term immunosuppression requirements and donor pancreas shortages. An ideal alternative source of islets would be from autologous precursor cells. The aim of this study was to determine whether the spleen can produce insulin-producing cells (IPCs) in our established model of pancreatic development. METHODS: Embryonic quail spleens (day 4.5) and chick pancreatic epithelium (day 4) were microdissected and recombined in a ratio of 1:1 (n = 12), 2:1 (n = 9) and 2:2 (n = 5). They were cultured for 7 days, sectioned, and analysed by fluorescent immunochemistry. Controls were performed to ensure clean separation. RESULTS: Overall, 12 (46%) of 26 recombinants contained IPCs of splenic origin, occurring in 5 (42%) of 12 of the of 1 spleen-1 epithelium recombinants, 3 (33%) of 9 of the 2 spleen-1 epithelium recombinants, and 4 (80%) of 5 of the 2 spleen-2 epithelia recombinants. Controls were negative. CONCLUSIONS: Preliminary results suggest developing avian spleens can differentiate into IPCs. Increased tissue mass enhanced the likelihood of this occurring. Mesenchyme-to-epithelia ratio did not influence this. The spleen could be an ideal autologous islet source for transplantation in children.
Authors: Francisco Dieguez-Acuña; Shohta Kodama; Yoshiaki Okubo; Ana Cristina Paz; Steven P Gygi; Denise L Faustman Journal: Int J Biochem Cell Biol Date: 2009-12-18 Impact factor: 5.085
Authors: Lai Wang; Mingjie Yang; Ana Arias; Lei Song; Fuqiang Li; Fang Tian; Minghui Qin; Ada Yukht; Ian K Williamson; Prediman K Shah; Behrooz G Sharifi Journal: PLoS One Date: 2015-06-03 Impact factor: 3.240