Scientists at a US biotechnology company implanted immature beta-cells derived from human embryonic stem cells (hES cells) into mice and showed that they generated insulin-secreting cells that responded to raised blood sugar. They hope the discovery will one day lead to a renewable source of insulin-producing cells for the treatment of diabetes.

The study is published in the early online 20 February issue of Nature Biotechnology and is the work of Emmanuel E Baetge and colleagues from Novocell Inc, based in San Diego, California.

The loss of pancreatic beta-cells is typical of type 1 diabetes, and some forms of type 2. Insulin produced by these cells helps to control blood sugar (glucose).

Scientists have already shown it is possible to implant humans with islets from donated pancreases to help control diabetes, but the supply of donor tissue is not enough to meet the demand. A renewable supply of human beta-cells would be a great help to the development of cell therapies for diabetes, said the authors.

Human islets, or more accurately islets of Langerhans, are clusters of hormone and enzyme producing cells in the pancreas, an organ that is about the size of a hand and situated just behind the lower stomach. Islets are made of several types of cells, including insulin-producing beta-cells.

In this study Baetge and colleagues implanted immature beta-cells produced from hES cells into mice whose beta-cells had been chemically destroyed (this effectively created diabetes-like conditions in the mice).

Within three months, when the implanted mice were given glucose, they responded in a similar way to mice that had been implanted with 3,000 human islets. This was shown by testing circulating levels of human insulin and C-peptide (a byproduct of insulin production in the pancreas).

Baetge, who is chief scientific officer at Novocell, told the media:

“They are producing all the right enzymes and release insulin in response to glucose.”

The researchers found that the new insulin-expressing cells showed many other properties of functional beta-cells, such as expression of beta-cell transcription factors (their DNA was behaving like beta-cell DNA), appropriate processing of proinsulin (a key stage in insulin production), and the presence of “mature endocrine secretory granules”.

A final test proved the therapeutic potential, because the implanted hES-derived beta-cells protected against induced hyperglycemia (high blood sugar).

Baetge and colleagues concluded that:

“Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.”

Director of Research at Diabetes UK, Dr Iain Frame, told the Daily Mail that people should not raise their hopes just yet. This study used mice whose insulin producing islet cells had been chemically destroyed, which is very different to the way type 1 diabetes occurs in humans, where the immune system destroys the beta-cells.

He said the researchers had not produced fully functioning islet cells, just one part, the beta-cells that produce insulin. This was a step forward, but not a major leap, he said.

“Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.”
Evert Kroon, Laura A Martinson, Kuniko Kadoya, Anne G Bang, Olivia G Kelly, Susan Eliazer, Holly Young, Mike Richardson, Nora G Smart, Justine Cunningham, Alan D Agulnick, Kevin A D’Amour, Melissa K Carpenter & Emmanuel E Baetge.
Nature Biotechnology Published online: 20 February 2008.

Click here for Abstract.

Click here to learn more about islets transplantation (American Diabetes Association).

Sources: Nature Biotechnology abstract, Washington Post, Daily Mail, National Diabetes Information Clearing House.

Written by: Catharine Paddock, PhD