Robertson Stuart A, Rowan-Hull Autumn M, Johnson Paul R V
Paediatric Surgical Research Laboratory, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom.
J Pediatr Surg. 2008 Feb;43(2):274-8. doi: 10.1016/j.jpedsurg.2007.10.013.
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.
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.
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.
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.
背景/目的:胰岛移植有望在糖尿病确诊后不久逆转病情,且在成人中已取得相当大的成功。其在儿童中的应用受到长期免疫抑制需求和供体胰腺短缺的限制。理想的胰岛替代来源将是自体前体细胞。本研究的目的是在我们已建立的胰腺发育模型中确定脾脏是否能产生胰岛素分泌细胞(IPCs)。
对胚胎期鹌鹑脾脏(4.5日龄)和鸡胰腺上皮(4日龄)进行显微解剖,并按1:1(n = 12)、2:1(n = 9)和2:2(n = 5)的比例重组。将它们培养7天,切片,并通过荧光免疫化学分析。进行对照以确保完全分离。
总体而言,26个重组体中有12个(46%)含有脾脏来源的IPCs,在1个脾脏-1个上皮重组体的12个中有5个(42%)出现,2个脾脏-1个上皮重组体的9个中有3个(33%)出现,2个脾脏-2个上皮重组体的5个中有4个(80%)出现。对照组为阴性。
初步结果表明,发育中的禽类脾脏可分化为IPCs。组织量增加会提高这种情况发生的可能性。间充质与上皮的比例对此没有影响。脾脏可能是儿童移植的理想自体胰岛来源。