Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism.
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 resolve...
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doaj-ac9e4dea76914cc4b864d4487b65b2262021-03-03T20:33:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022235010.1371/journal.pone.0222350Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism.Sophie G KellawayKarolina MosinskaZainaba MohamedAlexander RyanStephen RichardsonMelanie NewbouldIndraneel BanerjeeMark J DunneKaren E CosgroveCongenital 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.https://doi.org/10.1371/journal.pone.0222350 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie G Kellaway Karolina Mosinska Zainaba Mohamed Alexander Ryan Stephen Richardson Melanie Newbould Indraneel Banerjee Mark J Dunne Karen E Cosgrove |
spellingShingle |
Sophie G Kellaway Karolina Mosinska Zainaba Mohamed Alexander Ryan Stephen Richardson Melanie Newbould Indraneel Banerjee Mark J Dunne Karen E Cosgrove Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. PLoS ONE |
author_facet |
Sophie G Kellaway Karolina Mosinska Zainaba Mohamed Alexander Ryan Stephen Richardson Melanie Newbould Indraneel Banerjee Mark J Dunne Karen E Cosgrove |
author_sort |
Sophie G Kellaway |
title |
Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
title_short |
Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
title_full |
Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
title_fullStr |
Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
title_full_unstemmed |
Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
title_sort |
increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0222350 |
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