“Liposuction leftovers” easily converted to induced pluripotent stem cells

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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, according to a new study from Stanford’s School of Medicine. The findings were published online Monday in the Proceedings of the National Academy of Sciences.

“We’ve identified a great natural resource,” said Stanford surgery professor and co-author of the research, Michael Longaker, 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 cardiologist 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.”

Longaker is the deputy director of Stanford’s Stem Cell Biology and Regenerative Medicine Institute and director of children’s surgical research at Lucile Packard Children’s Hospital. Wu is an assistant professor of cardiology and radiology, and a member of Stanford’s Cardiovascular Institute (…)

Even those of us who are not obese would probably be happy to part with a couple of pounds (or more) of flab. Nestled within this unwanted 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 (…)

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 iPS cells but about 0.2 percent of the fat stem cells did so — a 20-fold improvement inefficiency.

The new iPS 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 (…)

from http://news.xinhuanet.com/english/2009-09/08/content_12011915.htm

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Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells

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Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. However, the low efficiency and slow kinetics of the reprogramming process have hampered progress with this technology. Here we report that a natural compound, vitamin C (Vc), enhances iPSC generation from both mouse and human somatic cells. Vc acts at least in part by alleviating cell senescence, a recently identified roadblock for reprogramming.

In addition, Vc accelerates gene expression changes and promotes the transition of pre-iPSC colonies to a fully reprogrammed state. Our results therefore highlight a straightforward method for improving the speed and efficiency of iPSC generation and provide additional insights into the mechanistic basis of the reprogramming process.► Vitamin C improves the speed and efficiency of mouse iPSC generation ► Adding vitamin C converts pre-iPSCs to iPSCs ► Vitamin C alleviates the senescence roadblock to reprogramming ► Human iPSC generation is also improved by vitamin C

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Possible cancer-causing genes taked off from engineered stem cells

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Whitehead Institute researchers have developed a novel method of removing potential cancer-causing genes during the reprogramming of skin cells from Parkinson’s disease patients into an embryonic-stem-cell-like state. Scientists were then able to use the resulting induced pluripotent stem (iPS) cells to derive dopamine-producing neurons, the cell type that degenerates in Parkinson’s disease patients.

The work marks the first time researchers have generated human iPS cells that have maintained their embryonic stem-cell-like properties after the removal of reprogramming genes. The findings are published in the March 6 edition of the journal Cell.

Removing the reprogramming genes is also important because of those genes’ effect on an iPS cell‘s gene expression (a measure of which genes the cell is using and how much it’s using those genes). When the researchers compared the gene expressions of human embryonic stem cells to iPS cells with and without the reprogramming factors, iPS cells without the reprogramming genes had a gene expression closer to human embryonic stem cells than to the same iPS cells that still contained the reprogramming genes.

“The reprogramming factors are known to bind to and affect the expression of 3,000 genes in the entire genome, so having artificial expression of those genes will change the cell’s overall gene expression,” Dirk Hockemeyer, who is also a co-author of the Cell article. “That’s why the four reprogramming genes can mess up the system so much. From now on, it will be tough for researchers to leave the reprogramming genes in iPS cells.”

from http://web.mit.edu/newsoffice/2009/parkinsons-stem-0305.html

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Embryonic stem cells, reprogrammed skin cells have inherent differences

Kathrin Plath

UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

The data from the study suggest that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures. The differing signatures were evident regardless of where the cell lines were generated, the methods by which they were derived or the species from which they were isolated, said William Lowry, a researcher with the Broad stem cell research center and a study author.

“We need to keep in mind that iPS cells are not perfectly similar to embryonic stem cells,” said Lowry, an assistant professor of molecular, cell and developmental biology. “We’re not sure what this means with regard to the biology of pluripotent stem cells. At this point our analyses comprise just an observation. It could be biologically irrelevant, or it could be manifested as an advantage or a disadvantage.”

The study appears in the July 2 issue of the journal Cell Stem Cell.

The iPS cells, like embryonic stem cells, have the potential to become all of the tissues in the body. However, iPS cells don’t require the destruction of an embryo. Some have touted iPS cells as replacements for embryonic stem cells. However, this study finds they are not identical as previously surmised. Researchers have maintained it is important to continue to study both cell types.

The study was a collaboration between the labs of Lowry and UCLA researcher Kathrin Plath. Lowry and Plath were among the first scientists worldwide and the first in California to reprogram human skin cells into iPS cells. The researchers performed microarray gene expression profiles on embryonic stem cells and iPS cells to measure the expression of thousands of genes at once, creating a global picture of cellular function.

Lowry and Plath noted that, when the molecular signatures were compared, it was clear that certain genes were expressed differently in embryonic stem cells than they were in iPS cells. They then compared their data to that stored on a National Institutes of Health data base, submitted by laboratories worldwide. They analyzed that data to see if the genetic profiling conducted in other labs validated their findings, and again they found overlapping but distinct differences in gene expression, Lowry said.

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Aging-related gene plays role in stem cell differentiation

Researchers from the Center for Stem Cell Biology and Regenerative Medicine and the Department of Medicine at Thomas Jefferson University claim that a gene shown to play a role in the aging process appears to play a role in the regulation of the differentiation of embryonic stem cells.

In the study, published online in the journal Aging Cell, the researchers identified a protein interaction that controls the silencing of Oct4, a key transcription factor that is critical to ensuring that embryonic stem cells remain pluripotent. The protein, WRNp, is the product of a gene associated with Werner syndrome, an autosomal recessive disorder hallmarked by premature aging. The gene expression in Werner syndrome closely resembles that of normal aging, and as a result, Werner syndrome is an accepted model of aging.

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