Writing in a new study, US researchers said it was easier and just as safe to make stem cells from fat cells freshly isolated from patients, for instance from cells present in liposuction “leftovers”, than it was to make them from skin cells as other studies have done recently.

The study was the work of researchers at the Stanford University School of Medicine in California and was published online ahead of print on 8 September in the Proceedings of the National Academy of Sciences, PNAS.

Ready sources of adult stem cells that can be reprogrammed to work like embryonic stem cells are a much sought important alternative to using embryos for making patient-specific cell lines to study diseases and regenerate tissue.

The Stanford researchers discovered that the globs of human fat removed during liposuction contain versatile cells that can be coaxed into becoming pluripotent (iPS) stem cells more easily than the skin cells that are often used by researchers.

Stanford surgery professor and co-author of the study, Dr Michael Longaker, referred to liposuction leftovers as “liquid gold” when he told the media:

“We’ve identified a great natural resource.”

Longaker is the deputy director of Stanford’s Stem Cell Biology and Regenerative Medicine Institute and also director of children’s surgical research at Lucile Packard Children’s Hospital at Stanford.

Senior author and cardiologist Dr Joseph Wu said 30 to 40 per cent of people in the US are obese, suggesting it would not be difficult to source fat cells to make iPS cells. Even people who are not obese might be happy to part with a couple of pounds of “flab”, suggested the researchers.

Wu also explained why it was easier to use fat cells than skin cells:

“Not only can we start with a lot of cells, we can reprogram them much more efficiently,” said Wu, who is an assistant professor of cardiology and radiology, and a member of Stanford’s Cardiovascular Institute.

“Fibroblasts, or skin cells, must be grown in the lab for three weeks or more before they can be reprogrammed. But these stem cells from fat are ready to go right away,” he added.

Another advantage is that the fat cells can be converted into iPS cells without using mouse-derived “feeder cells”, which are needed in the skin cell approach to grow the cells outside the body.

Some medical professionals worry that using animal derived feeder cells introduces the risk of cross-species contamination, so removing this step may make the fat derived iPS cells a more attractive option for developing human therapies, said the researchers in a press statement.

iPS cells from fat cells also have another advantage over skin cell derived iPS cells said the researchers: they are more versatile. The fat in our bellies is held in a lattice of fat cells and collagen, among which can be found multipotent cells called adipose, or fat, stem cells. These are not like specialized skin-cell fibroblasts in that they have a wider portfolio of differentiation options: they can become fat, bone, or muscle.

First author and postdoctoral scholar Dr Ning Sun, who carried out the research in Longaker’s and Wu’s labs, said:

“These cells are not as far along on the differentiation pathway, so they’re easier to back up to an earlier state.”

“They are more embryonic-like than fibroblasts, which take more effort to reprogram,” he added.

To reprogram cells and turn them into iPS cells researchers insert four genes called Yamanaka factors (after Shinya Yamanaka who first did this successfully at Kyoto University in 2006). These genes are normally unexpressed, or expressed at a very low level, in adult cells.

When Sun was reprogramming the fat stem cells he found they already had a higher starting level for expressing two of the four genes than adult skin cells. And when he added the Yamanaka factors, only 1 in 10,000 of the skin-cell fibroblasts turned into iPS cells, compared with 2 in 1,000 of the fat stem cells, showing a 20-fold increase in conversion efficiency.

The team also put the new iPS cells through what has now become a standard test of pluripotency. When injected into mice whose immune systems had been knocked out, they formed teratomas, a type of tumor, and they differentiated into cells of the three main tissue types in the body: neurons, muscle and epithelium.

The researchers are carrying on with the work to explore the genetic profile of these fat cells and find out if it is possible to reprogram them to become any type of cell in the body.

Longaker said:

“The idea of reprogramming a cell from your body to become anything your body needs is very exciting.”

“The field now needs to move forward in ways that the Food and Drug Administration would approve — with cells that can be efficiently reprogrammed without the risk of cross-species contamination — and Stanford is an ideal place for that to happen,” he added.

Wu gave an example of the possibilities that this research has opened up:

“Imagine if we could isolate fat cells from a patient with some type of congenital cardiac disease.”

“We could then differentiate them into cardiac cells, study how they respond to different drugs or stimuli and see how they compare to normal cells. This would be a great advance,” he added.

“Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells.”
Ning Sun, Nicholas J. Panetta, Deepak M. Gupta, Kitchener D. Wilson, Andrew Lee, Fangjun Jia, Shijun Hu, Athena M. Cherry, Robert C. Robbins, Michael T. Longaker, and Joseph C. Wu.
PNAS, published online before print September 8, 2009.
DOI:10.1073/pnas.0908450106

Source: Stanford School of Medicine.

Written by: Catharine Paddock, PhD