Gene Therapy Stimulates Replication of Insulin-Producing Cells

Diabetes researchers have discovered a method for stimulating the replication of human insulin-producing pancreatic beta cells in laboratory culture and after implantation into a mouse model.

Investigators at the University of Pittsburgh School of Medicine (PA, USA) examined the genomes of human and mouse beta cells. They found that human beta cells express a gene for the production of significant amounts of cdk-6 (cyclin-dependent protein kinase), while this protein was absent in mouse beta cells. To further increase the levels of cdk-6 in the human cells, the investigators used an adenovirus vector to transfect them with additional cdk-6 genes. In some experiments, the concentration of cyclin D1 protein was also increased by gene transplantation.

Results published in the January 9, 2009, online edition of the journal Diabetes revealed that in tissue culture high levels of cdk-6 and cyclin D1 caused marked activation of retinoblastoma protein phosphorylation and cell cycle progression, with no induction of cell death.

Human beta cells transduced with cdk-6 and cyclin D1 were transplanted into nonobese diabetic – severe combined immune-deficient (NOD-SCID) mice. These modified cells markedly outperformed native human beta cells by maintaining glucose control in the diabetic mice for the entire six weeks of study.

"Most scientists thought that these important pancreatic cells could not be induced to regenerate, or could only replicate very slowly," explained senior author Dr. Andrew F. Stewart, professor of medicine at the University of Pittsburgh School of Medicine. "This work provides proof-of-principle that the production of human beta cells can be stimulated, and that the newly generated cells function effectively both in the lab and in a living animal."

The investigators believe that being able to study human beta cells and their replication in vivo could greatly improve diabetes study models, and could lead to the development of techniques to generate new beta cells in patients with diabetes.

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University of Pittsburgh School of Medicine