Jeffery S Tessem | PubMed Health

PubMed2004

Roles for bone-marrow-derived cells in beta-cell maintenance.

With more than 177 million people suffering from diabetes worldwide, and the number expected to double by 2030, finding new ways to treat this disease is a high priority. Intensive effort is being directed towards developing mechanisms for increasing beta-cell expansion as a diabetic therapeutic. Recent studies, in which adult bone marrow has been used to induce beta-cell expansion in mice, have shown both exciting and controversial results. In these reports, marrow-derived cells can contribute towards beta-cell maintenance both by promoting endogenous beta-cell expansion and possibly by transdifferentiation into beta-cells. These studies reveal mechanisms for potential therapeutic intervention.

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PubMed2003

The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss.

Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1-/-E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.

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