The porcine islet-derived organoid showed the characteristics as pancreatic duct

Sci Rep. 2024 Mar 16;14(1):6401. doi: 10.1038/s41598-024-57059-1.

Abstract

Organoid is a tissue-engineered organ-like structure that resemble as an organ. Porcine islet-derived organoid might be used as an alternative donor of porcine islet xenotransplantation, a promising therapy for severe diabetes. In this study, we elucidated the characteristics of porcine islet organoids derived from porcine islets as a cell source for transplantation. Isolated porcine islets were 3D-cultured using growth factor-reduced matrigel in organoid culture medium consist of advanced DMEM/F12 with Wnt-3A, R-spondin, EGF, Noggin, IGF-1, bFGF, nicotinamide, B27, and some small molecules. Morphological and functional characteristics of islet organoids were evaluated in comparison with 2D-cultured islets in advanced DMEM/F12 medium. Relatively short-term (approximately 14 days)-cultured porcine islet organoids were enlarged and proliferated, but had an attenuated insulin-releasing function. Long-term (over a month)-cultured islet organoids could be passaged and cryopreserved. However, they showed pancreatic duct characteristics, including cystic induction, strong expression of Sox9, loss of PDX1 expression, and no insulin-releasing function. These findings were seen in long-term-cultured porcine islets. In conclusion, our porcine islet organoids showed the characteristics of pancreatic ducts. Further study is necessary for producing porcine islet-derived organoids having characteristics as islets.

Keywords: Islet; Organoid; Pancreas; Pancreatic duct; Pig; Transplantation.

MeSH terms

  • Animals
  • Insulin / metabolism
  • Islets of Langerhans Transplantation*
  • Islets of Langerhans* / metabolism
  • Organoids / metabolism
  • Pancreatic Ducts / metabolism
  • Swine
  • Tissue Engineering

Substances

  • Insulin