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A novel approach to increase human islet cell mass while preserving beta-cell function
Gillian M Beattie1, Anthony M P Montgomery, Ana D Lopez
1Department of Pediatrics and Surgery, The Whittier Institute, University of California at San Diego, 9894 Genesee Avenue, La Jolla, CA 92037, USA.
Diabetes
|November 28, 2002
Summary
Human beta-cells can be expanded in fibrin gels using hepatocyte growth factor (HGF), maintaining function for transplantation. This method preserves glucose responsiveness and enhances graft size and function in vivo.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Endocrinology
Background:
- Human islet expansion in monolayer culture results in loss of function and senescence.
- Maintaining the three-dimensional (3-D) configuration of islets is crucial for preserving beta-cell function.
Purpose of the Study:
- To investigate the feasibility of expanding human beta-cells in fibrin gels using hepatocyte growth factor (HGF).
- To assess the preservation of glucose responsiveness and in vivo function after transplantation of expanded islets.
Main Methods:
- Human islets were cultured in fibrin gels and as free-floating cultures, with and without growth factors and nicotinamide.
- Proliferation, insulin content, and glucose-stimulated insulin release were measured in vitro.
- Islet graft size, endocrine cell composition, and circulating C-peptide levels were assessed in vivo after transplantation into nude mice.
Main Results:
- Significant beta-cell proliferation and a threefold increase in total insulin were observed only in islets cultured in fibrin gels with the growth factor cocktail.
- Physiologic glucose responsiveness was preserved in vitro.
- Transplantation of islets cultured in fibrin gels resulted in larger grafts with higher insulin and glucagon content and increased circulating human C-peptide levels compared to free-floating islets.
Conclusions:
- Fibrin gel culture enables hepatocyte growth factor (HGF)-mediated human beta-cell expansion while preserving cell-cell contacts and glucose responsiveness.
- Limited ex vivo islet expansion in fibrin gels may improve recipient-donor tissue ratios, potentially leading to functional outcomes comparable to whole-organ transplants.