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Title: Pancreatic small cells: Analysis of quiescence, long-term maintenance and insulin expression in vitro

Abstract

We have previously identified a novel population of small cells in human and canine pancreas characterized by immature morphology, quiescence, and a glucose-responsive insulin secretion. Based on their immature phenotype and predominant presence in small islets, we have hypothesized that small cells serve as islet progenitors. This hypothesis remains untested, however, due to persistent quiescence and scarcity of small cells in vitro. We have recently developed a culture medium that allowed for modest small cell proliferation. In this study we characterized the expression of genes potentially involved in small cell growth regulation by Q-RT-PCR. Our results suggest that quiescence of small cells correlates with up-regulation of Cdk inhibitors p27{sup Kip1}, p16{sup INK4a} and p21{sup CIP1}, PTEN, Hep27 and Foxo1a and with down-regulation of c-Myc and the receptors for EGF, FGF2 and HGF. The exit from quiescence correlates with activation of EGFR expression and down-regulation of p27{sup Kip1} and p16{sup INK4a}. We also report here that small cells can be maintained in long-term non-adherent cultures preserving insulin and glucagon production for up to 208 days. Therefore, expansion of small cells in vitro may have a significant potential for the treatment of diabetes. This study is an important step in understanding themore » mechanisms involved in small cell growth regulation, which is required to fully evaluate their functional potential.« less

Authors:
 [1];  [2];  [2];  [3]
  1. Department of Surgery, McGill University and Research Institute of the McGill University Health Center, 1650 Cedar Ave, Montreal, Quebec, H3G1A4 (Canada). E-mail: maria.petropavlovskaia@mail.mcgill.ca
  2. Pharmaceutical Production Research Facility (PPRF), Faculty of Engineering, University of Calgary, Calgary, Alberta, T2N1N4 (Canada)
  3. Department of Surgery, McGill University and Research Institute of the McGill University Health Center, 1650 Cedar Ave, Montreal, Quebec, H3G1A4 (Canada)
Publication Date:
OSTI Identifier:
20972128
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 5; Other Information: DOI: 10.1016/j.yexcr.2006.12.012; PII: S0014-4827(06)00506-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; CULTURE MEDIA; DOGS; GENE REGULATION; GENES; GLUCAGON; GLUCOSE; IN VITRO; INSULIN; MORPHOLOGY; PANCREAS; PHENOTYPE; POLYMERASE CHAIN REACTION; RECEPTORS

Citation Formats

Petropavlovskaia, M., Bodnar, C.A., Behie, L.A., and Rosenberg, L. Pancreatic small cells: Analysis of quiescence, long-term maintenance and insulin expression in vitro. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.12.012.
Petropavlovskaia, M., Bodnar, C.A., Behie, L.A., & Rosenberg, L. Pancreatic small cells: Analysis of quiescence, long-term maintenance and insulin expression in vitro. United States. doi:10.1016/j.yexcr.2006.12.012.
Petropavlovskaia, M., Bodnar, C.A., Behie, L.A., and Rosenberg, L. Sat . "Pancreatic small cells: Analysis of quiescence, long-term maintenance and insulin expression in vitro". United States. doi:10.1016/j.yexcr.2006.12.012.
@article{osti_20972128,
title = {Pancreatic small cells: Analysis of quiescence, long-term maintenance and insulin expression in vitro},
author = {Petropavlovskaia, M. and Bodnar, C.A. and Behie, L.A. and Rosenberg, L.},
abstractNote = {We have previously identified a novel population of small cells in human and canine pancreas characterized by immature morphology, quiescence, and a glucose-responsive insulin secretion. Based on their immature phenotype and predominant presence in small islets, we have hypothesized that small cells serve as islet progenitors. This hypothesis remains untested, however, due to persistent quiescence and scarcity of small cells in vitro. We have recently developed a culture medium that allowed for modest small cell proliferation. In this study we characterized the expression of genes potentially involved in small cell growth regulation by Q-RT-PCR. Our results suggest that quiescence of small cells correlates with up-regulation of Cdk inhibitors p27{sup Kip1}, p16{sup INK4a} and p21{sup CIP1}, PTEN, Hep27 and Foxo1a and with down-regulation of c-Myc and the receptors for EGF, FGF2 and HGF. The exit from quiescence correlates with activation of EGFR expression and down-regulation of p27{sup Kip1} and p16{sup INK4a}. We also report here that small cells can be maintained in long-term non-adherent cultures preserving insulin and glucagon production for up to 208 days. Therefore, expansion of small cells in vitro may have a significant potential for the treatment of diabetes. This study is an important step in understanding the mechanisms involved in small cell growth regulation, which is required to fully evaluate their functional potential.},
doi = {10.1016/j.yexcr.2006.12.012},
journal = {Experimental Cell Research},
number = 5,
volume = 313,
place = {United States},
year = {Sat Mar 10 00:00:00 EST 2007},
month = {Sat Mar 10 00:00:00 EST 2007}
}