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

Journal Article · Sat Mar 10 00:00:00 EST 2007 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.12.012· OSTI ID:20972128

Petropavlovskaia, M ^[1]; Bodnar, C A ^[2]; Behie, L A ^[2]; Rosenberg, L ^[1]

---

1. Department of Surgery, McGill University and Research Institute of the McGill University Health Center, 1650 Cedar Ave, Montreal, Quebec, H3G1A4 (Canada)
2. Pharmaceutical Production Research Facility (PPRF), Faculty of Engineering, University of Calgary, Calgary, Alberta, T2N1N4 (Canada)

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.

• OSTI ID: 20972128
• Journal Information: Experimental Cell Research, Vol. 313, 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); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
CULTURE MEDIA
DOGS
GENE REGULATION
GENES
GLUCAGON
GLUCOSE
IN VITRO
INSULIN
MORPHOLOGY
PANCREAS
PHENOTYPE
POLYMERASE CHAIN REACTION
RECEPTORS