Distributions of endocrine cell clusters during porcine pancreatic development

PLoS One. 2019 May 10;14(5):e0216254. doi: 10.1371/journal.pone.0216254. eCollection 2019.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cluster Analysis
  • Diabetes Mellitus / therapy
  • Endocrine Cells / cytology*
  • Humans
  • Islets of Langerhans / cytology
  • Islets of Langerhans / growth & development*
  • Islets of Langerhans Transplantation / methods*
  • Nerve Tissue Proteins / metabolism
  • Swine
  • Transplantation, Heterologous / methods*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins

Associated data

  • figshare/10.6084/m9.figshare.8050301

Grants and funding

This research work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (17K10527 to M.N.), the Japan Agency for Medical Research and Development (Leading Advanced Projects for Medical Innovation [LEAP] Generation of Functional Organs using Developmental Niche), the Ministry of Health, Labour and Welfare of Japan, and grants from the Technology Agency and the Meiji University International Institute for Bio-Resource Research (H.N.). The funding organizations had no roles in the study’s design, data collection and analysis, the decision to publish, or the manuscript’s preparation.