�US scientists have observed a style to transmute living pancreatic cells in mice into another type of cellphone that produces insulin without having to
revert to the stem cell stage, creating what is now a third route for cell reprogramming to add to the existing methods of iPS (induced pluripotent stem cells) and hES (human
embryologic stem cells).
The study was the work of Harvard Stem Cell Institute co-director Doug Melton and post doctoral fellow Qiao "Joe" Zhou , at Harvard University,
Boston, Massachusetts, and colleagues and was published as an advanced online paper in Nature on 27th August.
Melton and colleagues seem to have got attained the "holy grail" of stem cell research, they have turned unitary type of adult mobile phone directly into another type
of grownup cell, opening the door to living cell transformation directly in patients.
Using what they called "direct reprogramming," the researchers turned exocrine gland cells, which account for around 95 percent of pancreatic tissue paper, into
rarefied insulin-producing beta cells, which account for a a great deal smaller 1 per centime or less of pancreatic cells and are consequently very precious. Beta cells
are the ones that die off in Type I diabetes.
The feat is being heralded as a major step in developing treatments for Type 2 and Type 1 diabetes, bringing closer the day when patients won't have
to be checking their blood simoleons all the time, or even get hold of insulin medication. The researchers did nonetheless caution that it will be some time earlier
this is a world, and there are many difficult hurdle race to get over before the method prat be tried in humans.
For example, as with iPS, Melton's team used viruses to introduce various arranging factors (bits of DNA that change the way that genes express
themselves) into the target cells. This is a speculative approach in humans because the viruses could behave in former unplanned and unpredictable shipway.
The researchers are looking for safer alternatives based on chemicals for this reason.
Melton pointed out that direct reprogramming will not remove the need for iPS and hES, and said his lab will continue to use them as well as the new
techniques.
"We need to attack problems from multiple angles," said Melton.
The researchers had a bit of luck when they ascertained they could directly reprogram adult cells. Usually, as in iPS, you have to usage hundreds of
trascription factors to return a mature cell back into a pluripotent cell that can buoy then be encouraged to develop into any one of a range of cells. If you
were lucky to pick the right combination of a much littler subset of transcription factors, in theory you should be able to short circuit the iPS route
and go straight from one type of get on cell to another.
That is what happened with Melton's team. With a heady mix of luck and two days of unvarying trial and error they hit on three arrangement factors,
Ngn3, Pdx1, and MafA. They just unbroken asking themselves the interrogation "What genes do you have to turn on for the cell to become a beta
cell?"
As Melton commented:
"If you want to do reprogramming it doesn't take smashing insight to figure tabu that the key genes are transcription factors - the proteins that bind DNA
and tell cells which genes to turn on and which to turn off."
He said that a stem turn cell goes through many steps before it becomes a especial type of adult cadre, each step is like passing through a door with a
specific lock in and each lock is a trascription factor. He and his team asked themselves which "locks" were in the beta cells, and that gave them 1,C
possible arrangement factors. Eventually they ascertained that only 200 of them are expressed in the cells of the pancreas, so that helped to narrow
the field of study somewhat.
The future step was to retrieve which of the 200 were special to pancreatic cells that surrounded the beta cells, and that brought the number down to a
more realizable 28. The 28 became 9 after the did further "linage studies", as Joe explained, "my best guess is it's these nine". And he was
right. They then mixed all 9 and injected them into the pancreas. Then by removing them one by one they discovered it worked best when only three
transcription factors were present, the other six-spot weren't as important, said Joe.
The fate of destiny came when they chose those 9, because if they had not produced results, Melton and his team would have given up, they
said.
Through the experiment Melton and colleagues were capable to show that the newly induced beta-cells were "indistinguishable from endogenous islet
beta-cells in size, shape and ultrastructure".
They expressed genes essential for beta-cell function and were able to "ameliorate hyperglycemia by remodelling local vasculature and secreting
insulin".
The researchers concluded that:
"This study provides an exercise of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cellular phone
reprogramming without reversion to a pluripotent stem cadre state."
"In vivo reprogramming of adult pancreatic exocrine cells to beta-cells."
Qiao Zhou, Juliana Brown, Andrew Kanarek, Jayaraj Rajagopal & Douglas A. Melton
Nature Advance published on-line 27 August 2008.
doi:10.1038/nature07314
Click here for
Abstract.
Sources: Journal Abstract, Harvard Medical School.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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Monday 8 September 2008
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