Dual origin, development, and fate of bovine pancreatic islets

Dual origin, development, and fate of bovine pancreatic islets
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牛胰岛的双重起源、发育和命运

DOI:
10.1111/joa.12014
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发表时间:
2013
期刊:
影响因子:
2.4
通讯作者:
Ricken A.M.
Ricken A.M.
中科院分区:
医学3区
文献类型:
--
作者:
Merkwitz C;Lochhead P;Böttger J;Matz-Soja M;Sakurai M.Gebhardt R;Ricken A.M.

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内分泌细胞在牛胰腺发育的早期阶段是明显的,此时胰腺仍由原始上皮索组成。在这个阶段,内分泌细胞散布在前体细胞之间,这些前体细胞注定要形成后来的外分泌小叶的导管-腺泡树。我们在此证明,在冠臀长≥ 11 cm的胎牛中,内分泌细胞通过组装成两个在组织发生、结构和命运上不同的单位而逐渐与发育中的外分泌胰腺分离。少量的“小叶周围巨胰岛”与大量的“小叶内小胰岛”是可以区分的。这两种类型的胰岛从导管树的末端平行出现。除了数量、位置和大小的差异外,巨胰岛和小胰岛在细胞组成(主要是胰岛素合成细胞vs.内分泌细胞的混合物)、形态(具有脑回状和玫瑰花状外观的上皮小梁vs.内分泌细胞的紧凑圆形排列)以及它们与胰腺内神经节和神经的关系方面也存在差异。在产前期间,进一步的差异变得明显;虽然“小叶间小胰岛”持续存在于小牛和成年牛的胰腺中,但小叶周围巨大胰岛会退化,其特征在于实质退化、广泛出血、白细胞浸润(骨髓和T细胞)和进行性纤维化替代。总之,导管-腺泡树的上皮前体细胞可能产生具有不同组织形态学、细胞组成和命运的胰岛群体。当使用这些细胞产生用于移植治疗的胰岛时,应考虑到这一点。
Endocrine cells are evident at an early stage in bovine pancreatic development when the pancreas still consists of primitive epithelial cords. At this stage, the endocrine cells are interspersed between the precursor cells destined to form the ductulo‐acinar trees of later exocrine lobules. We here demonstrate that, in bovine fetuses of crown rump length ≥ 11 cm, the endocrine cells become increasingly segregated from the developing exocrine pancreas by assembly into two units that differ in histogenesis, architecture, and fate. Small numbers of ‘perilobular giant islets’ are distinguishable from larger numbers of ‘intralobular small islets’. The two types of islets arise in parallel from the ends of the ductal tree. Aside from differences in number, location, and size, the giant and small islets differ in cellular composition (predominantly insulin‐synthesising cells vs. mixtures of endocrine cells), morphology (epithelial trabeculae with gyriform and rosette‐like appearance vs. compact circular arrangements of endocrine cells), and in their relationships to intrapancreatic ganglia and nerves. A further difference becomes apparent during the antenatal period; while the ‘interlobular small islets’ persist in the pancreata of calves and adult cattle, the perilobular giant islets are subject to regression, characterised by involution of the parenchyma, extensive haemorrhage, leukocyte infiltration (myeloid and T‐cells) and progressive fibrotic replacement. In conclusion, epithelial precursor cells of the ductolo‐acinar tree may give rise to populations of pancreatic islets with different histomorphology, cellular composition and fates. This should be taken into account when using these cells for the generation of pancreatic islets for transplantation therapy.