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A Novel Approach to Increase Human Islet Cell Mass While Preserving β-Cell Function
Ist Teil von
Diabetes (New York, N.Y.), 2002-12, Vol.51 (12), p.3435-3439
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2002
Quelle
MEDLINE
Beschreibungen/Notizen
A Novel Approach to Increase Human Islet Cell Mass While Preserving β-Cell Function
Gillian M. Beattie 1 ,
Anthony M.P. Montgomery 1 ,
Ana D. Lopez 1 ,
Ergeng Hao 1 ,
Brandon Perez 1 ,
Margaret L. Just 1 ,
Jonathan R.T. Lakey 2 ,
Marquis E. Hart 1 and
Alberto Hayek 1
1 Department of Pediatrics and Surgery, The Whittier Institute, University of California at San Diego, La Jolla, California
2 Surgical Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada
Abstract
Human islet expansion in monolayer culture leads to loss of function and senescence. By maintaining the 3-D configuration
of islets in fibrin gels, it is feasible to expand β-cells in response to hepatocyte growth factor (HGF) while preserving
physiologic glucose responsiveness both in vitro and in vivo after transplantation into nude mice. Islets were cultured free
floating with or without growth factors and nicotinamide and in fibrin gels with the same conditions. Proliferation was observed
only in islets cultured in fibrin gels and the cocktail; total insulin increased by threefold, with a concomitant increase
in β-cell mass by morphometry. Insulin release after glucose challenge was also preserved. Islets in fibrin gels gave rise
in vivo to large grafts rich in insulin and glucagon, and grafts from free-floating islets were smaller with fewer endocrine
cells. Circulating human C-peptide levels were higher than in the mice receiving free-floating islets. In summary, fibrin
allows for HGF-mediated cell proliferation while preserving glucose responsiveness in an environment that preserves cell-cell
contacts. Limited islet ex vivo expansion under these conditions may improve recipient-donor tissue ratios to equal the functional
results of whole-organ transplants.
Footnotes
Address correspondence and reprint requests to A. Hayek, MD, The Whittier Institute-UCSD Department of Pediatrics, 9894 Genesee
Ave., La Jolla, CA 92037. E-mail: ahayek{at}ucsd.edu .
Received for publication 26 June 2002 and accepted in revised form 19 August 2002.
HGF, hepatocyte growth factor; SF, scatter factor.
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