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Teasing out tissue from blood

It would be the ultimate in tissue therapy. Simply supply a bag of your blood and come back two weeks later to find it turned into cells from other tissues, ranging from brain and liver cells to the insulin-producing beta islet cells of the pancreas.

The idea is to revert a patient’s blood cells to the stem cell stage and then chemically nudge them to re-specialise into particular tissue types that can be implanted to heal damaged tissue. A huge advantage over using donated tissue is that the transplant would be "autologous" – made of the patient’s own cells, thus avoiding immune rejection.

"It’s autologous, we don’t need to worry about rejection of tissue, and immunosuppression," says Glenn Winnier of Pharmafrontiers, a company in Woodland, Texas. It now claims to have refined a way to produce stem cells from white blood cells called monocytes and develop them into many different tissue types including, crucially, insulin-producing cells.

Most mainstream stem cell researchers are sceptical, however, because the idea that specialised cells like monocytes can be "de-differentiated" back to more primitive stem cells remains heretical. "Let’s see first how they perform functionally," says Stephen Minger of King’s College London.

Pharmafrontiers is to present its latest results at the end of this month in Toronto at the International Society for Stem Cell Research meeting. Deriving "stem cells" from monocytes was originally reported in 2003 in Proceedings of the National Academy of Sciences (vol 100, p 2426) by a team at Argonne National Laboratory in Illinois, but Pharmafrontiers bought up and refined the technology.

The company says it can de-differentiate monocytes into "multipotent" stem cells by exposing them to certain nutrients and growth factors. Such stem cells can give rise to many but not all tissue types like "pluripotent" embryonic stem cells (ESCs). Different combinations of growth factors can then turn the stem cells into a range of cell types.

Moreover, Pharmafrontiers says it is about to submit a patent application on a brew that turns the monocytes into pancreatic islet-like cells that produce insulin in response to high levels of glucose. "We now want to transplant these cultures into a diabetic mouse model," says Winnier, adding their results are being prepared for publication in a peer-reviewed journal.

Alan Colman of ES International, a company developing insulin-producing cells from human ESCs in Singapore, is also sceptical. He says it would take huge amounts of blood to produce enough islet cells for individual patients.

Chris Major of University College London says most stem cell researchers have neglected the idea of de-differentiating adult cells in favour of using embryonic stem cells. However, he warned there could be problems with using adult cells, because they have suffered years of genetic damage. "With embryonic cells, they’re fresh, and not corrupted," he says.

Other teams are also experimenting with stem cells from blood. A team led by Bernat Soria of the Institute of Bioengineering at Miguel Hernández University in Alicante, Spain, last year reported reversing a mouse form of diabetes with insulin-producing cells developed from blood cells (Gastroenterology, vol 128, p 1774). And researchers at the University of Kiel in Germany led by Fred Fandrich report producing liver cells.

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