The spleen--a potential source of new islets for transplantation?
OBJECTIVE
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.
Robertson
Stuart A
SA
Paediatric Surgical Research Laboratory, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom.
Rowan-Hull
Autumn M
AM
Johnson
Paul R V
PR
D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D002642:Chick Embryo; D002678:Chimera; D004625:Embryo, Nonmammalian; D004848:Epithelium / Q000196:embryology*; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000196:embryology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D023421:Models, Animal; D010179:Pancreas / Q000196:embryology; D011784:Quail; D012016:Reference Values; D012680:Sensitivity and Specificity; D013154:Spleen / Q000166:cytology
D007328:Insulin