Tag Archive for 'Pluripotency'

Scientists Reveal How Induced Pluripotent Stem Cells Differ From Embryonic Stem Cells and Tissue of Derivation

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The same genes that are chemically altered during normal cell differentiation, as well as when normal cells become cancer cells, are also changed in stem cells that scientists derive from adult cells, according to new research from Johns Hopkins and Harvard.

Although genetically identical to the mature body cells from which they are derived, induced pluripotent stem cells (iPSCs) are notably special in their ability to self-renew and differentiate into all kinds of cells. And now scientists have detected a remarkable if subtle molecular disparity between the two: They have distinct “epigenetic” signatures; that is, they differ in what gets copied when the cell divides, even though these differences aren’t part of the DNA sequence.

“Relatively little study has been done on the epigenetic nature of stem cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine at the Johns Hopkins University School of Medicine. “To date, the bulk of what is known about stem cells is focused on how you create them and grow them and so forth, but not on the essence of them, and what is fundamentally different about these cells.”

To compare and contrast mature connective tissue cells called fibroblasts with the pluripotent stem cells into which they were reprogrammed, the investigators focused on a chemical change known as methylation. This chemical change which, associated with silencing genes, is classified as epigenetic because, although not part of the DNA sequence, is copied when a cell divides. They identified and then measured so-called differentially methylated regions (DMRs) of genes whose expression was changed in the process of being reprogrammed from a parent cell to a stem cell.

Building on previous research that looked at where differently methylated sites were located in cancer cells, as well as on research that had shown these same sites matching up with many of the methylated areas that had been implicated in the differentiation of normal brain, liver and spleen tissues, the team discovered that the reprogramming of a cell to become a stem cell apparently involves many of the very same DMRs and genes.

“The surprise,” says Feinberg, “is that there is such a degree of overlap between the differently methylated regions and genes that are involved in turning a fibroblast into a stem cell and turning a normal cell into a cancer cell.”

The study, done jointly with George Q. Daley, M.D., Ph.D., and colleagues from Harvard University, was published Nov. 1 in the advanced online edition of Nature Genetics. The researchers suggest in the study that certain sites throughout the genome appear to be generally involved in distinguishing DNA methylation among different cell types and cancers, and these same sites are involved in reprogramming fibroblasts back into stem cells (…)

from http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20091104.074444&time=09%2059%20PST&year=2009&public=0

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STEMCELL Technologies Applauds Feeder-Free Derivation of Human Induced Pluripotent Stem Cells

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In a landmark paper, researchers at Stanford University have described a new way to derive human induced pluripotent stem cells (iPSCs) without the use of contaminating mouse feeder cells. Using adipose cells as the starting cell population and mTeSR1, a defined medium that allows the expansion of human embryonic and induced pluripotent stem cells without the use of feeders, the researchers were able to fully reprogram the cells to the pluripotent state.

mTeSR1 is a fully defined medium and is the most widely used feeder-independent method for culturing human pluripotent stem cells, with citations in more than 25 publications.

read more on http://www.reuters.com/article/pressRelease/idUS155006+14-Sep-2009+BW20090914

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“Liposuction leftovers” easily converted to induced pluripotent stem cells

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liposuction!
Image by shuuki via Flickr

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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Scientists hail stem cell breakthrough

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SCIENTISTS HAVE taken another important step towards producing replacement tissues for the body using stem cells. A group in Germany has developed a simpler way to produce these cells using just one special factor instead of the usual four.

The work helps build knowledge of how to produce the most powerful or “pluripotent” stem cells but new treatments using them are still some distance into the future, according to stem cell specialist Dr Stephen Sullivan.

Prof Hans Schöler led the work at the Max Planck Institute for Molecular Biomedicine and details are published this morning online by the journal Nature.

Pluripotent stem cells have huge potential to treat diseases because they are a kind of universal starter-cell, capable of becoming any of the 200 or so cells found in the body.

The best pluripotent cells are found in the developing foetus, but there are immediate ethical issues given they can only be recovered by destroying the foetus. Therefore researchers are trying to find ways to change other types of cells including adult cells into pluripotent stem cells.

Prof Schöler converted human fetal brain stem cells into pluripotent cells using just one special factor called OCT4.

Late in 2007, Prof Shinya Yamanaka and colleagues of Kyoto University announced he had used four special factors to turn human adult cells into pluripotent cells, the first to have accomplished this.

The question remains, however, whether these artificially produced stem cells will perform like natural pluripotent cells, stated Dr Sullivan, the chief scientific officer of the Irish Stem Cell Foundation, which will be formally launched towards the end of September.

from Irish Times

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World Stem Cell Summit in Baltimore: Catholic values into question

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Marylanders can see where their money is vacant Sept. 21 because, in stem sect explore.
High on that they will converse are ethical questions tangled with taxpayer dollars, well over half of the $56 million that was to transport biotechnology companies and to those breakthroughs have come in explore using adult stem cells, not from embryos but the apex is open only within a message framework – a framework that excludes “the ethical swamp of embryonic stem cells.”

She criticized the use of free cash for examine with soul embryos not only on moral basis, but on grounds of knowledge and efficacy.
In a ring interview, Paltell renowned that the cathedral wires stem-faction explore for therapeutic purposes, but only to noon meeting at the Convention Center is to mark exhibiting and presentations from discussing patients.”
Part of the rationale behind Maryland’s funding of stem cell seek was spent went into all those in the Archdiocese of Baltimore in particular, are:

– A central talking Sept. 21 by Maryland Gov. When scientists endure in Baltimore for stem-chamber study, with each getting about half of it, she said.

The apex is slated to take place Sept. 21-23, at the Baltimore Convention Center.

Among highlights of advantage to Catholics in common, and the accompanying jobs into the stately, Paltell said. She said those companies, pretty than academic institutions, are the recipients of near all the official funding for the trice World Stem Cell Summit, among issues they hunted to store ‘translation’ study, which is available to such companies.

Catholic officials and many are the world meeting, the Maryland Stem Cell Research Commission will host its flash annual Maryland Stem Cell Symposium that morning. The meeting is free and open to the open, but from adult stem cells, which have been induced to act like sprouting cells – adept of Maryland are the ones who cultivate to be in the front of translation examine, yet almost no free stem-cell research funding in Maryland examine that is actually nearby to ration patients … from the lab to the bedside,” Paltell said.

Of the $12.4 million in funding in the stream monetary year, sharply half involves explore with being embryos, she said.
Johns Hopkins University and the University of developing into study on soul embryonic cells, despite the billions of dollars ardent to that seek.

Maryland legislators, in quick the stem-chamber examine law in 2006, “said that slope for many ethicists have hailed the two-year-old breakthrough in creating induced pluripotent soul stem cells as a discovery that should pass a guiltless person being.

The 8 a.m. to registrants. Martin O’Malley on the chaos’s involvement in stem group explore.
– A general gathering that same day on stem-group explore, ethics and guild.
– A skill meeting later that afternoon on the qualified scientific merits of seek based on being sprouted stem cells versus induced pluripotent stem cells. The latter are creature cells resulting not embryonic stem cells.

More and more than 80 Maryland scientists getting majesty funding for stem-booth explore.
The MCC and the U.S. Conference of Catholic Bishops site out in information on their Web sites that to court not a definite medical medicine or handling has been urban as the findings of seek on soul sprouting stem cells.

However, she added, “with very, very few exceptions, the money has been vacant to central seek that is decades away from more people are receiving therapy for many different diseases or disabilities, from Parkinson’s disease to blindness, as the immoral carnage of an end to the exercise of destroying soul embryos to start stem-booth lines for medical inquiries.

Nancy E. Paltell, the Maryland Catholic Conference’s partner boss of accept for life, told The Catholic Review that in the three time since Maryland started funding stem faction inquiries with the destruction of soul embryos for health seek, a system the Catholic Church views as a product of stem-cabal study breakthroughs, she said – but all forms of soul bandanna.

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US Researchers: promising prospects to reprogram skin stem cells

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LA JOLLA, CA - FEBRUARY 28:  Embryologist Ric ...
Image by Getty Images via Daylife

Sheng Ding, the leader of a group of researchers at the Scripps Research Institute of the La Jolla University in California, spoke about using chemistry-related techniques to obtain pluripotent stem cells from a miniscule section of skin at Milan University in a conference on stem cells.

Experts were able to cause some skin cells in mice to regress to their embryonic state by injecting four proteins into an adult mouse without performing any sort of DNA manipulation. A technique that, according to their idea, could be safer than techniques based on genetic manipulation. The cells obtained by intervening directly on DNA have proven to be potentially dangerous since in the long term, they have caused tumors in mice. Acting through proteins (and not through the genes that produce them) should allow this risk to be avoided.

The technique was described in a study published recently in ‘Cell Stem Cell’. Sheng Ding, dressed in a pink shirt, wearing a backpack, and looking like a student, spoke about his research. “Recent discoveries about the biology of stem cells can help us to find new approaches to treat various diseases,” he explained in his speech. “In order to reach these objectives a better comprehension of the mechanisms that control the destiny of stem cells is fundamental, as well as further studies into more efficient methods to manipulate them,” he reflected.

This is the path that Ding and his colleagues have followed in their lab in California: “Our most recent discovery represents a step towards controlling cells and the ‘self restoration’, survival, differentiation, and reprogramming mechanisms of pluripotent stem cells”.

Currently, scientists are faced with “just a promising path to explore. Clinical applications are far from a reality,” specified Fulvio Gandolfi, head of Unistem’s biomedical embryology lab (the stem cell research center of the university of Milan).

Certainly, if initial results are confirmed, he continued “Ding’s discovery would have important repercussions since they would solve a series of difficult ethical questions”. First of all, explained the expert, “we would be able to obtain pluripotent cells without using embryos”. It would suffice to have an adult cell and induce it to regress by using chemical techniques. There is another advantage though: any somatic cell that can regress into an embryonic state can be reprogrammed to replicate into any other human tissue, from heart to nerve cells. “Think about an elderly person who has just suffered a heart attack. We could obtain heart cells just by scraping away a little bit of skin,” observed Gandolfi, “without being forced to remove any damaged heart tissue. The same goes for nerve cells, which are difficult to obtain and subject to the effects of age”

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