Distributions of endocrine cell clusters during porcine pancreatic development

• Published in: PloS one Vol. 14; no. 5; p. e0216254
• Main Authors: Nagaya, Masaki, Hayashi, Asuka, Nakano, Kazuaki, Honda, Michiyo, Hasegawa, Koki, Okamoto, Kazutoshi, Itazaki, Shiori, Matsunari, Hitomi, Watanabe, Masahito, Umeyama, Kazuhiro, Nagashima, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.05.2019; Public Library of Science (PLoS)
• Subjects: Age; Age Factors; Agricultural production; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biology and Life Sciences; Brain architecture; Care and treatment; Clinical trials; Cluster Analysis; Clustering; Diabetes; Diabetes mellitus; Diabetes Mellitus - therapy; Diabetes therapy; Endocrine Cells - cytology; Engineering; Ethics; Gene expression; Genes; Growth; Hogs; Humans; Insulin; Islet cell transplantation; Islets of Langerhans - cytology; Islets of Langerhans - growth & development; Islets of Langerhans Transplantation - methods; Laboratories; Life sciences; Medicine and Health Sciences; Morphology; Nerve Tissue Proteins - metabolism; Neurogenins; Pancreas; Physiology; Povidone; Research and Analysis Methods; Retirement benefits; Spleen; Swine; Therapeutic applications; Transcription factors; Transplantation; Transplantation, Heterologous - methods; Transplants & implants; Xenografts; Xenotransplantation; Young adults; New Zealand; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216254

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.