(Journal Article): Proliferation and differentiation in the human fetal endocrine pancreas.
Bouwens L, Lu WG, De Krijger R (Laboratory of Experimental Pathology, Free University Brussels (V.U.B), Belgium.)
IN:
Diabetologia
1997; 40(4):398-404
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)
ABSTRACT: The morphogenesis and growth of the endocrine pancreas has not been well investigated in man although it represents an important issue in diabetology. We examined human fetal pancreas from 12 to 41 weeks of gestation immunocytochemically to evaluate proliferative activity with the Ki-67 marker, and cytodifferentiation with cytokeratin 19 (ductal cells), synaptophysin (all endocrine cells), and insulin, glucagon, somatostatin and pancreatic polypeptide (islet cell types). Ki-67 labelling was found in all these cell types but was much higher in ductal cells than in islet cells. An intermediate population expressed synaptophysin but lacked islet hormones. With increasing gestational age the Ki-67 labelling index decreased from 17 to 4% in ductal cells, from 9 to 1% in synaptophysin-positive cells, and from 3 to 0.1% in insulin- or glucagon-positive cells. From 12 to 16 weeks, all epithelial cells including the endocrine islet cells expressed cytokeratin 19. Thereafter cytokeratin 19 expression decreased and eventually disappeared from most islet cells, whereas strong expression remained in the ductal cells. We show that differentiated human islet cells have only very limited proliferative capacity, and we demonstrate the existence of transitional differentiation stages between ductal and islet cells.
TYPE OF PUBLICATION: Original article
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(Journal Article): Dynamics of beta-cell mass in the growing rat pancreas.
Finegood DT, Scaglia L, Bonner-Weir S (Elliot P. Joslin Research Laboratories, Joslin Diabetes Center, Boston, Massachusetts.)
IN:
Diabetes
1995; 44(3):249-256
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)
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ABSTRACT: The growth and development of the endocrine pancreas has been studied for many years, but questions remain concerning the regulation of the mass of insulin-producing beta-cells both in the normal growing pancreas and during the pathogenesis of diabetes. The homeostatic control of beta-cell mass in both normal and pathophysiological conditions is based on the balance of cell proliferation, cell growth, and cell death. To gain insight into the relative contribution of each of these dynamic processes, we first mathematically analyzed the data available on the components involved in the maintenance of beta-cell mass, including rates of replication, beta-cell volume, and the beta-cell mass itself, at various ages in normal Sprague-Dawley rats. Then these data were combined in a simple mass balance equation to construct a mathematical model of the dynamics of the beta-cell mass in the normal growing rat pancreas. Such a model has allowed us to infer the contributions of fluxes that cannot be measured, i.e., neogenesis and cell death, to the known mass of beta-cells. Another important contribution of this model is to raise unanswered questions concerning the control of the balance of cell death and cell renewal in the endocrine pancreas.
TYPE OF PUBLICATION: Original article
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(Journal Article): Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact.
Beattie GM, Rubin JS, Mally MI, Otonkoski T, Hayek A (Whittier Institute, Department of Pediatrics, University of California San Diego, La Jolla 92037, USA.)
IN:
Diabetes
1996; 45(9):1223-1228
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)
ABSTRACT: Ex vivo expansion of human fetal pancreatic endocrine cells is important for biological studies and as a potential tissue source for transplantation in insulin-deficient states. In tissue culture experiments involving the use of hepatocyte growth factor/scatter factor and selected extracellular matrices, we obtained a 30-fold increase in cell number of human fetal pancreatic epithelial cells. This proliferation in monolayer culture was associated with marked downregulation of insulin and glucagon gene expression. However, gene expression increased when the cells were combined into three-dimensional aggregates, suggesting that cell-cell contact mediated mechanisms regulate the transcription of islet-specific genes, a process enhanced by nicotinamide (NIC). After transplantation into nude mice, either as cell suspensions or aggregates, only the cell aggregates treated with NIC developed into mature functional islet-like structures. These are the first experiments to describe the interactions of specific matrices and growth factors in the ex vivo expansion of human fetal pancreatic cells, and they also show the importance of cell aggregates in the context of cellular and molecular events that might positively influence islet cell transplantation.
TYPE OF PUBLICATION: Original article
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