Jayanthi N V G, Rowan-Hull A M, Teague W J, Johnson P R V
Paediatric Surgical Research Laboratory, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
Transplant Proc. 2005 Oct;37(8):3485-6. doi: 10.1016/j.transproceed.2005.09.026.
Stem or progenitor cells are a promising potential alternative source of pancreatic islets for transplantation in the treatment of juvenile-onset diabetes. However, to derive islets from such cells, it is important to elucidate the mechanisms of normal pancreatic development. Previous work in our laboratory has shown that, contrary to previous thinking, pancreatic mesenchyme when combined with pancreatic epithelium can contribute cells to islets. However, the signals and role of individual tissues involved in this mesenchyme-to-epithelial transition (MET) have yet to be elucidated. The aim of this study was to investigate whether MET can occur in the absence of pancreatic epithelium. Chick and quail eggs were incubated for 4 days and the dorsal pancreatic buds and stomach rudiments were microdissected. Mesenchyme and epithelium of the organ rudiments were separated after collagenase treatment. Separated pancreatic mesenchyme were cultured alone and in combination with stomach (nonpancreatic). After 7 days of culture, the specimens were analysed using immunohistochemistry for quail-specific nucleolar antigen (QCPN), insulin, and islet precursor cell marker (ISL-1). Pancreatic mesenchyme when cultured in the absence of epithelium did not differentiate into islets, but differentiated into fibroblast-like cells. When pancreatic mesenchyme were cultured in combination with stomach epithelium, there was no evidence of mesenchymally derived islets. We have demonstrated that pancreatic mesenchyme require pancreatic epithelium to differentiate into islet cells. These findings further increase our understanding of normal pancreatic islet development and may help to elucidate the molecular mechanisms of MET in islet development.
干细胞或祖细胞是一种很有前景的潜在替代胰岛来源，可用于移植治疗青少年型糖尿病。然而，要从这类细胞中获得胰岛，阐明正常胰腺发育的机制很重要。我们实验室之前的研究表明，与之前的观点相反，胰腺间充质与胰腺上皮结合时可向胰岛贡献细胞。然而，参与这种间充质 - 上皮转变（MET）的各个组织的信号和作用尚未阐明。本研究的目的是调查在没有胰腺上皮的情况下MET是否会发生。将鸡和鹌鹑蛋孵化4天，然后显微解剖背侧胰腺芽和胃原基。用胶原酶处理后，将器官原基的间充质和上皮分离。分离出的胰腺间充质单独培养，并与胃（非胰腺）联合培养。培养7天后，使用免疫组织化学方法分析标本中的鹌鹑特异性核仁抗原（QCPN）、胰岛素和胰岛前体细胞标志物（ISL-1）。在没有上皮的情况下培养的胰腺间充质不会分化为胰岛，而是分化为成纤维细胞样细胞。当胰腺间充质与胃上皮联合培养时，没有间充质来源胰岛的证据。我们已经证明，胰腺间充质需要胰腺上皮才能分化为胰岛细胞。这些发现进一步加深了我们对正常胰岛发育的理解，并可能有助于阐明胰岛发育中MET的分子机制。
