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2009-09-08 11:35:03 | Weblog
[naturenews] from [nature.com]

[naturenews]
Published online 7 September 2009 | Nature | doi:10.1038/news.2009.883
News
Flab and freckles could advance stem cell research

Alternative tissues shown to yield reprogrammed cells aplenty.
By Elie Dolgin


Fat cells and pigment-producing skin cells can be reprogrammed into stem cells much faster and more efficiently than the skin cells that are usually used — suggesting large bellies and little black moles could provide much-needed material for deriving patient-specific stem cells.

"More than one type of adult somatic cell can serve as a target for reprogramming to a pluripotent state," says William Lowry, a stem-cell biologist at the University of California, Los Angeles, who was not involved in the research. "You don't have to use fibroblasts. There are other possibilities."

Reprogramming human skin cells remains woefully inefficient; typically, it takes about a month for 1 in 10,000 fibroblast skin cells to give rise to induced pluripotent stem (iPS) cells. Such iPS cells can, like embryonic stem cells, develop into any cell type. So researchers have been on the lookout for tissue types that can more speedily and easily be turned pluripotent. Several alternative human cells have been shown to work — including blood, hair, bone marrow, and neural stem cells — but most have these have not boosted success rates. One exception is hair-like keratinocytes plucked from a baby's foreskin1, but this is an unsuitable source for adult patients.

Now, a pair of research groups have generated iPS cells from two easily obtainable cell types in half the time and with much-improved success rates. In one study, reported online today in the Proceedings of the National Academy of Sciences, a team led by Joseph Wu and Michael Langaker at Stanford University School of Medicine in California converted fat tissue into iPS cells2. In the other, published last week in the Journal of Cell Science, Konrad Hochedlinger and his colleagues at the Massachusetts General Hospital in Boston reprogrammed melanocytes, the skin cells that produce pigmented skin3.

Fat chance

The Stanford researchers used liposuction to extract a couple litres of fat from the bellies of four overweight individuals aged 40 to 65. They then treated the tissue to remove all the gooey, globular fat, leaving behind a collection of fat tissue stem cells. Unlike standard techniques, which require about a month to culture skin biopsies to populations large enough for the reprogramming process, the fat tissue was ready to go after two days of pretreatment.

What's more, the cellular reprogramming took only two more weeks and was 20-times more efficient than when converting fibroblasts using the same technique. "We basically shave off six to eight weeks compared to what the other guys are doing with fibroblasts," says Wu, who is now working to find safer ways to reprogram fat without using viruses.

{“This is thus far the most efficient and effective cell type yet to be described.”
Ron Evans
Salk Institute}

"This is thus far the most efficient and effective cell type yet to be described for generation" of iPS cells, says Ron Evans, a molecular physiologist at the Salk Institute in La Jolla, California, who has "eerily similar" unpublished results, due to be published in PNAS, showing that more than 1% of fat cells can be turned pluripotent.

Wu and his colleagues also created the first human iPS cells using a slightly tweaked protocol that did not involve mouse "feeder" cells, which nurture the tissue with supportive proteins but can lead to contamination with animal products — a big no-no for therapeutic purposes. "That eliminates a number of problems years from now when we try to translate this work into the clinic," says Farshid Guilak, a tissue engineer at the Duke University Medical Center in Durham, North Carolina.

Skin deep

The poor chances of successfully reprogramming skin fibroblasts also led Hochedlinger's team to look for alternative sources. The researchers found that melanocytes undergo reprogramming after just 10 days and with five-fold greater success rates compared with fibroblasts.

Despite the improved efficiencies, Lowry doubts that many researchers will abandon skin cells in favour of fat cells or melanocytes. Huge banks of skin cells and bone marrow cells already exist, he says, so "you're probably going to stick with what you already have access to".

Langaker disagrees. "There's a lot of fat in America, unfortunately, and it's a renewable source of cells," he says. "I believe that the number of cells you get from fat and how quickly you're ready to go with them is a huge strategic advantage."

References
1. Aasen, T. et al. Nat. Biotechnol. 26, 1276-1284 (2008). | Article | PubMed | ChemPort |
2. Sun, N. et al. Proc. Natl. Acad. Sci. USA advance online publication doi:10.1073/pnas.0908450106 (2009).
3. Utikal, J., Maherali, N., Kulalert, W. & Hochedlinger, K. J. Cell Sci. adv
ance online publication doi:10.1242/jcs.054783 (2009).


[naturenews]
Published online 7 September 2009 | Nature | doi:10.1038/news.2009.888
News
Nobelist's brain institute wins reprieve
Court prevents host from pulling the p
lug on cash-strapped Italian research lab.

By Alison Abbott

A civil court in Rome has ordered the Santa Lucia Foundation not to shut off any more amenities to an institute founded by centenarian Nobel laureate Rita Levi-Montalcini — for the moment, at least.

The foundation had planned to cut off supplies of carbon dioxide and compressed air, essential for tissue culture, today, and disconnect all electricity from the European Brain Research Institute (EBRI) by the end of the month. But now the injunction forces it to hold off.

The judge requested on Saturday that the foundation try to reach an agreement with EBRI before a second hearing on 23 September.

The institute began work in Rome in 2005 after a competition to identify a host. It was intended to bypass Italy's sluggish bureaucracy and create the sort of scientifically competitive environment rare in life sciences in the country.

{“EBRI has unfortunately never made payments on time.”
Luigi Amadio
Santa Lucia Foundation}

The Santa Lucia Foundation, which also runs a private hospital in Rome, won the competition, in part by offering 10 years' rent-free accommodation in a new building. EBRI, now home to 28 research groups, is required only to pay expenses — around €500,000 per year.

Levi-Montalcini's 100th birthday earlier this year was marked with national celebrations in Italy. But EBRI has not won the political support that she anticipated and has struggled financially.

Now the foundation wants to terminate the contract. Its director general, Luigi Amadio, requested advance payment of this year's expenses instead of retrospective payment. EBRI objected at first, but completed payments by July.

The foundation nonetheless proclaimed EBRI "not financially sustainable". During July it cut off telephones, stopped cleaning contracts and severed electricity connections to rooms containing –80 °C freezers.

Amadio says that in the past couple of years, "EBRI has unfortunately never made payments on time".

Empty promises?

When the affair became public last week, research minister Mariastella Gelmini declared her intention to find a solution. Gelmini had promised the institution a gift of €500,000 during Levi-Montalcini's birthday celebrations, but this has not yet materialized.

{“This all happened very suddenly and has left people confused.”
Alberto Bacci
European Brain Research Institute}

Amadio says that the Santa Lucia Foundation has received at least €50 million less than it was entitled to in reimbursement from the region of Lazio, which includes Rome, for the clinical activities of its hospital in recent years, and this is why it has to cut costs. "If this problem were to be resolved positively, the foundation could re-examine a possible new agreement with EBRI," he says.

But the regional president of Lazio, Piero Marrazzo, says that the foundation has received all it is due, and that it should not mix issues relating to hospital financing with its research activities. Marrazzo has also offered general support to EBRI and says he is prepared to help negotiate a solution.

Scientists at the institute are meanwhile treading water. Neuroscientist Alberto Bacci, who won one of the first European Research Council large and prestigious Starting Independent Researchers Grants in 2007, says he trusts that a solution will be found but admits that things are not easy.

"This all happened very suddenly and has left people confused," he told Nature. "But I am trying to carry on working and to keep morale high."

"All the parties will meet this week in the research ministry to try to work things out," says Piergiorgio Strata, the science director of EBRI. "There was no reason to evict us on short notice like this."

In the meantime, the region of Piedmont and the University of Turin have offered to host EBRI if it should lose its home, says Strata, himself a professor at the university.

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