According to new research, globs of human fat removed during liposuction conceal versatile cells that are more quickly and easily coaxed to become induced pluripotent stem cells, or iPS cells, than are the skin cells most often used by researchers.

"We've identified a great natural resource," said Michael Longaker, co author of the research, who has called the readily available liposuction leftovers "liquid gold." Reprogramming adult cells to function like embryonic stem cells is one way researchers hope to create patient-specific cell lines to regenerate tissue or to study specific diseases in the laboratory.

"Thirty to 40 percent of adults in this country are obese," agreed Joseph Wu, the paper's senior author. "Not only can we start with a lot of cells, we can reprogram them much more efficiently. 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."

These cells can be converted without the need for mouse-derived "feeder cells", potentially making them an ideal starting material for human therapies. Feeder cells are often used when growing human skin cells outside the body with the risk that cross-species contamination could make them unsuitable for human use.

Contained within the latticework of fat cells and collagen are multipotent cells called adipose, or fat, stem cells. Unlike highly specialized skin-cell fibroblasts, these cells in the fat have a relatively wide portfolio of differentiation options, becoming fat, bone or muscle as needed. It's this pre-existing flexibility, the researchers believe, that gives these cell an edge over the skin cells.

"These cells are not as far along on the differentiation pathway, so they're easier to back up to an earlier state," said first author Ning Sun, who conducted the research. "They are more embryonic-like than fibroblasts, which take more effort to reprogram."

These reprogrammed induced pluripotent stem cells cells are usually created by expressing four genes, called Yamanaka factors, normally unexpressed (or expressed at very low levels) in adult cells.

Sun found that the fat stem cells actually express higher starting levels of two of the four reprogramming genes than do adult skin cells, suggesting that these cells are already primed for change. When he added all four genes, about 0.01 percent of the skin-cell fibroblasts eventually became induced pluripotent stem cells cells but about 0.2 percent of the fat stem cells did so, a 20-fold improvement in efficiency.

The new induced pluripotent stem cells cells passed the standard tests for pluripotency: They formed tumors called teratomas when injected into immunocompromised mice, and they could differentiate into cells from the three main tissue types in the body, including neurons, muscle and gut epithelium. The researchers are now investigating whether the gene expression profiles of the fat stem cells could be used to identify a subpopulation that could be reprogrammed even more efficiently.

"The idea of reprogramming a cell from your body to become anything your body needs is very exciting," said Longaker.
References:
1. Ning Sun, et al. Stanford University Medical Center.

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