Meiji University International Institute for Bio-Resource Research, Kawasaki, Japan.
Department of Immunology, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
PLoS One. 2019 May 10;14(5):e0216254. doi: 10.1371/journal.pone.0216254. eCollection 2019.
Pancreatic islet xenotransplantation is a potential treatment for diabetes mellitus, and porcine pancreas may provide a readily available source of islets. Islets in juvenile pigs are smaller than those in young adult pigs, but the insulin content is very similar. In addition, as juvenile pigs are more easily reared in uncontaminated conditions, many researchers have conducted studies using pancreatic islets from juvenile pigs. We aimed to analyze the distributions of endocrine cell clusters by comprehensively evaluating juvenile porcine pancreatic development and to propose an appropriate age at which islets could be isolated from the juvenile porcine pancreas.
Splenic (SL) and duodenal lobe (DL) samples were collected from the pancreases of pigs aged 0-180 days (n = 3/day after birth). The chronological changes in endocrine cell clustering were analyzed in relation to morphological changes, cell characterization, numbers, islet areas, and gene expression.
In juvenile pigs aged 0-21 days, the pancreas contained numerous endocrine cells, and compact islets appeared from 21 days of age. Well-defined small islets were seen at 28 days of age, and the clusters were denser in the SL than in the DL. At 35 days of age, the islets were morphologically similar to those observed at 180 days of age, and the greater number of islets was similar to that seen at 90 days of age. The differences in the islets' cytoarchitecture between the lobes were negligible. The expression of β-cell-related genes was higher in the juvenile pancreas than in the adult pancreas, and the expression of neurogenin-3 decreased dramatically over time.
These findings may have implications for attempts to refine the most appropriate age for islet isolation from porcine donors. Focusing on porcine pancreatic islets isolated at around 35 days after birth may offer benefits regarding their xenotransplantation potential.
胰岛异种移植是治疗糖尿病的一种有潜力的方法，而猪胰腺可能提供了一个易于获得的胰岛来源。幼年猪的胰岛比青年猪的胰岛小，但胰岛素含量非常相似。此外，由于幼年猪更容易在无污染的环境中饲养，许多研究人员已经使用幼年猪的胰岛进行了研究。我们旨在通过全面评估幼年猪胰腺的发育情况，分析内分泌细胞簇的分布，并提出从幼年猪胰腺中分离胰岛的合适年龄。
从 0-180 天大的猪的胰腺中采集脾（SL）和十二指肠叶（DL）样本（出生后每天采集 3 个样本）。分析内分泌细胞簇的时空变化与形态变化、细胞特征、数量、胰岛面积和基因表达的关系。
在 0-21 天大的幼年猪中，胰腺含有大量的内分泌细胞，从 21 天大开始出现致密的胰岛。在 28 天大可以看到定义明确的小胰岛，且在 SL 中比在 DL 中更密集。在 35 天大，胰岛的形态与 180 天大的相似，胰岛的数量比 90 天大的多。两个叶之间的胰岛细胞结构差异可以忽略不计。β细胞相关基因在幼年胰腺中的表达高于成年胰腺，神经基因-3的表达随时间显著下降。
这些发现可能对尝试改进从猪供体中分离胰岛的最佳年龄具有重要意义。关注大约在出生后 35 天分离的猪胰腺胰岛，可能在其异种移植潜力方面具有优势。
