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Flab and freckles could advance stem cell research

September 7, 2009 By Elie ED Dolgin This article courtesy of Nature News.

Alternative tissues shown to yield reprogrammed cells aplenty.

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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).
  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. advance online publication doi:10.1242/jcs.054783 (2009).

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