Ali Yusuf, Diez Juan, Selander Lars, Zheng Xiaofeng, Edlund Helena, Berggren Per-Olof
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636 921, Republic of Singapore.
Diabetologia. 2016 May;59(5):1007-11. doi: 10.1007/s00125-016-3883-x. Epub 2016 Feb 4.
AIMS/HYPOTHESIS: In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development.
We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time.
The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation.
CONCLUSIONS/INTERPRETATION: Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.
目的/假设:由于胰腺组织难以接近,对发育中的胰腺进行体内成像具有挑战性。为了规避这一问题,在胚胎第10.5天(E10.5),我们将小鼠发育中的胰腺芽移植到眼房(ACE)中,以确定眼睛是否是支持胰腺发育的有用移植部位。
我们将E10.5期的背侧胰腺芽移植到同基因受体小鼠的眼房中。使用小鼠胰岛素启动子-绿色荧光蛋白(MIP-GFP)小鼠作为组织供体,我们以单个β细胞分辨率对胰腺芽随时间的发育进行了非侵入性成像。
移植到眼房中的胰腺芽迅速植入并血管化。胰腺祖细胞分化为外分泌和内分泌细胞,包括表达胰岛素、胰高血糖素和生长抑素的细胞。移植的胰腺芽的形态与天然发育中的胰腺相似。移植的胰腺芽内的β细胞对葡萄糖的反应方式与天然胎儿β细胞相似,且优于体外发育的β细胞。与体外培养的胰腺外植体不同,在眼房中发育的胰腺组织是血管化的,为发育中的胰腺组织提供了类似于天然情况的环境。
结论/解读:总之,我们表明眼房能够在体内随时间支持发育中的胰腺芽的生长、分化和功能。