Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism
Autoři:
Sophie G. Kellaway aff001; Karolina Mosinska aff001; Zainaba Mohamed aff002; Alexander Ryan aff001; Stephen Richardson aff001; Melanie Newbould aff003; Indraneel Banerjee aff002; Mark J. Dunne aff001; Karen E. Cosgrove aff001
Působiště autorů:
Faculty of Biology Medicine and Health, School of Medicine, Division of Diabetes Endocrinology and Gastroenterology, University of Manchester, Manchester, United Kingdom
aff001; Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, United Kingdom
aff002; Department of Paediatric Histopathology, Royal Manchester Children’s Hospital, Manchester, United Kingdom
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222350
Souhrn
Congenital hyperinsulinism (CHI) is characterised by inappropriate insulin secretion causing profound hypoglycaemia and brain damage if inadequately controlled. Pancreatic tissue isolated from patients with diffuse CHI shows abnormal proliferation rates, the mechanisms of which are not fully resolved. Understanding cell proliferation in CHI may lead to new therapeutic options, alongside opportunities to manipulate β-cell mass in patients with diabetes. We aimed to generate cell-lines from CHI pancreatic tissue to provide in vitro model systems for research. Three pancreatic mesenchymal stem cell-lines (CHIpMSC1-3) were derived from patients with CHI disease variants: focal, atypical and diffuse. All CHIpMSC lines demonstrated increased proliferation compared with control adult-derived pMSCs. Cell cycle alterations including increased CDK1 levels and decreased p27Kip1 nuclear localisation were observed in CHIpMSCs when compared to control pMSCs. In conclusion, CHIpMSCs are a useful in vitro model to further understand the cell cycle alterations leading to increased islet cell proliferation in CHI.
Klíčová slova:
Biology and life sciences – Cell biology – Cell processes – Cell cycle and cell division – Biochemistry – Hormones – Anatomy – Endocrine system – Exocrine glands – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Carbohydrates – Monosaccharides – Glucose – Organic chemistry – Medicine and health sciences – Endocrinology – Diabetic endocrinology – Insulin – Pancreas – Research and analysis methods – Spectrum analysis techniques – Spectrophotometry – Cytophotometry – Flow cytometry – Specimen preparation and treatment – Staining – Cell staining – Group-specific staining – Alizarin staining – Nuclear staining
Zdroje
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