City projects

Microencapsulation of insulin-producing cells is a platform technology Tuch believes will overcome many of the drawbacks of other islet transplantation studies, particular the obvious drawback of immune rejection.

And while the current trial uses islets from cadavers, it is obvious the technology can be used with a number of different sources of insulin-producing cells. The DTU is investigating a number of these in addition to the donor pancreases, including human embryonic stem cells; stem cells derived from cord blood, the nose and the fetal pancreas; animal pancreas, particular pig; and genetically modified cell lines.

The Sydney Project is aiming for the human embryonic stem cell approach. "The thrust of what we are doing now is what we call the Sydney Project, which says that by 2012 we will be in clinical trials with human embryonic stem cells which will be differentiating into insulin-producing cells," Tuch says.

Research groups around the world now have their own 'city projects' and have agreed to share data. Examination of the data show the DTU where it is compared to others and what is possible considered the resources it has.

"The Sydney Project is a dream but it is based upon reality in terms of where we are and where our 'competitors' are," Tuch says. "The rate of progress that has been made, and our peers' perception of our data, tells us it isn't pie in the sky."

The project has a number of issues to overcome in that time, the first being to convert embryonic stem cells into insulin producing cells, which Tuch says that Novocell in California has achieved. Then there are the issues of safety - avoiding tumours, preventing rejection and the regulatory issues that everyone the world over has to deal with in one way or another.

"This is why I think five years is not unreasonable," he says. "No human embryonic stem cell is used yet in a human trial, but Geron is about to start one as a therapy for spinal cord lesions. They've put in their application for regulatory approval and it is not hard to see how the dominoes are likely to fall in the next five years."

The DTU has a co-operative agreement with IVF Australia to produce human embryonic stem cell lines from spare fertilised eggs and has produced two such lines: Endeavour 1 and Endeavour 2, the first of which is being used and will soon be distributed by the UK's Stem Cell Bank. The team has been able to convert hESCs into pancreatic progenitors using a two-stage, eight-day culture protocol and further work is being done to develop the cells into surrogate insulin-producing ones.

It is also investigating reprogramming cells using somatic cell nuclear transfer to create patient- and disease-specific lines. The lack of availability of unfertilised eggs has led it to investigate a number of novel sources, including the use of eggs from women who are having their ovaries removed to reduce the risk of them developing ovarian cancer.

"That is in the process of gaining approval here in Australia so it is early days yet. Getting normal eggs from an IVF clinic is a very conjectural one ... you can get around that problem using animal eggs but that is not allowed in Australia yet."