Wisconsin Advanced Technology Advocates, Inc.

Reprogrammed cells retain some identity in embryonic state, study shows

By Mark Johnson of the Journal Sentinel

Posted: July 19, 2010 12:08 p.m.

Several years after scientists found a way to manipulate biology and send skin cells back to their embryonic origin, they are now learning that nature is not so easily tricked.

A reprogrammed skin cell retains a memory of its original identity as skin. Moreover, after the skin cell has returned to the embryonic state, it appears more willing to turn back into skin than to adopt a new identity.

The new findings by the lab of stem cell researcher George Daley at Children's Hospital Boston, were described Monday in a paper published online in the journal Nature and begin to address one of the mysteries surrounding reprogramming.

Since 2007 when the labs of James Thomson at University of Wisconsin-Madison and Shinya Yamanaka at Kyoto University first used a cocktail of genes to create an alternative to human embryonic stem cells, scientists have been puzzled by subtle differences between actual embryonic stem cells and these engineered versions.

The differences are important because the engineered cells were hailed as an alternative to embryonic stem cells that would allow scientists to make all of the cells in the human body while bypassing the ethical controversy that surrounded embryonic stem cells.

Daley said his team's work overthrows the assumption "that when you reprogram a skin or a blood cell you erase its memory of being skin or blood … Researchers have to appreciate the potential for this memory and erase it further or exploit it."

Full story.

Cellular Dynamics, Promega to collaborate on tests

By Kathleen Gallagher of the Journal Sentinel

Posted: June 15, 2010 10:08 a.m.

Cellular Dynamics International and Promega Corp. have entered into a research collaboration to develop toxicity tests for drug developers that use stem-cell derived heart cells.

The companies, both based in Madison, said the collaboration has potential to provide pharmaceutical company researchers with more predictive data, driving the development of safer and more effective drugs.

Their tests would use an alternative to embryonic stem cells known as iPS, or induced pluripotent stem cells that are made by Cellular Dynamics. To make iPS cells, Cellular Dynamics scientists take tissue cells, for example, and engineer them into cells that have all the characteristics of embryonic stem cells and are able to turn into beating heart cells, liver cells or any other cells in the body.

Full story.

Scientists create human embryonic stem cells with enhanced pluripotency

CAMBRIDGE, Mass. (May 3, 2010) – Whitehead Institute researchers have converted established human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells to a base state of greater pluripotency.

"This is a previously unknown pluripotent state in human cells," says Jacob Hanna, a postdoctoral researcher in the lab of Whitehead Member Rudolf Jaenisch. "It's the first time these cell types have approached the flexibility found in mouse ES cells."

ES cells and iPS cells have attracted much attention because of their potential to mature into virtually any cell type in the body. Because ethical and legal issues have hampered human ES cell research, mouse cells have provided a more viable platform for ES cell studies. However, mouse and human ES cells differ in a number of significant ways, raising the very real possibility that breakthroughs in mouse stem cell science simply won't be reproducible with human stem cells.

Researchers have had a relatively easy time genetically manipulating and preventing differentiation (maturation beyond the base pluripotent state) in mouse ES and iPS cells. But human ES and iPS cells have different sets of expressed genes and depend on different signaling pathways for growth and differentiation than mouse ES and iPS cells, which makes the human cells more difficult to work with.

Because of these biological differences, researchers refer to mouse ES and iPS cells as "naïve" while human ES and iPS cells, which teeter on the verge of maturation, are more mature and are referred to as being "primed" for differentiation.

Hanna thought this "primed" state of human cells might be attributable to the way the human ES cell lines are created and stored. To generate ES cell lines, researchers remove cells from an early-stage embryo, called a blastocyst. Once removed from this ball of 80-100 cells, the ES cells are put into serum with other cells to keep the ES cells alive and prevent them from differentiating.

WARF loses a round in stem cell patent dispute

By Kathleen Gallagher of the Journal Sentinel

Posted: May 3, 2010 11:50 a.m.

The Wisconsin Alumni Research Foundation has suffered a blow in its effort to protect a key patent for embryonic stem cell technology.

The U.S. Patent and Trademark Office last week reversed an earlier decision in which it rejected an appeal on one of three basic human embryonic stem cell patents held by the foundation, known as WARF.

The patent in question covers early work done by University of Wisconsin - Madison stem cell pioneer James Thomson. The patent office said it now agrees with the argument made by two foundations that Thomson's work covered by the single patent could have been performed by other scientists with access to the same resources.

The rejection does not affect a decision the patent office made in early 2008 to uphold two other basic embryonic stem cell patents held by WARF.

"WARF has been invited by the Board of Patent Appeals to continue prosecution of this application and plans to do so and vigorously pursue these claims with the patent office," the foundation said in a statement.

Full story.

Chemists influence stem-cell development with geometry

University of Chicago scientists have successfully used geometrically patterned surfaces to influence the development of stem cells. The new approach is a departure from that of many stem-cell biologists, who focus instead on uncovering the role of proteins in controlling the fate of stem cells.

"The cells are seeing the same soluble proteins. In both cases it's the shape alone that's dictating whether they turn into fat or bone, and that hasn't been appreciated before," said Milan Mrksich, Professor in Chemistry and a Howard Hughes Medical Institute Investigator, who led the study. "That's exciting because stem-cell therapies are of enormous interest right now, and a significant effort is ongoing to identify the laboratory conditions that can take a stem cell and push it into a specific lineage."

The UChicago team found that making cells assume a star shape promotes a tense cytoskeleton, which provides structural support for cells, while a flower shape promotes a looser cytoskeleton. "On a flower shape you get the majority of cells turning to fat, and on a star shape you've got the majority of cells turning into bone," said Kris Kilian, a National Institutes of Health Fellow in Mrksich's research group. The UChicago team published its findings in the March 1 Early Edition of the Proceedings of the National Academy of Sciences.

Mrksich cautioned that the method is far from ready for use in the harvest of stem cells for therapeutic use, but it does signal a potentially promising direction for further study.

Mrksich's research group has a long history of developing methods for patterning surfaces with chemistry to control the positions, sizes and shapes of cells in culture, and applying those patterned cells to drug-discovery assays, and studies of cell migration and cell adhesion.

Contact: Steve Koppes

s-koppes@uchicago.edu

773-702-8366

University of Chicago

UWM researcher's program helps predict stem cell fates

By Mark Johnson of the Journal Sentinel

Posted: Feb. 7, 2010

A software program developed by a University of Wisconsin-Milwaukee researcher successfully has predicted the fate of stem cells, a key step toward better understanding the developmental process and perhaps one day controlling it.

The program, developed by UWM's Andrew R. Cohen and described in a paper published Sunday in the journal Nature Methods, uses sophisticated mathematical techniques to study the movements of stem cells and translate those observations into reliable predictions about the kinds of cells they will eventually become.

Stem cells travel a path from less specific to more specific, from the limitless possibilities of an embryonic stem cell to the finished product - a piece of heart, brain, bone or skin. By studying the subtle behaviors that lead a cell to move toward one of these end points as opposed to the others, scientists hope they will discover ways to guide cells toward a particular path - perhaps skin to replace some that has been lost.

Full story.

Making Old Stem Cells Act Young Again

In virtually every part of the body, stem cells stand ready to replenish mature cells lost to wounds, disease, and everyday wear and tear. But like other cells, stem cells eventually lose their normal functions as they age, leaving the body less able to repair itself.

Surprisingly, this age-related decline in stem cell potency may be somewhat reversible. A team of Howard Hughes Medical Institute (HHMI) researchers has found that in old mice, a several-week exposure to the blood of young mice causes their bone marrow stem cells to act “young” again.

Full story.

Scientists convert cells while bypassing embryonic state

By Mark Johnson of the Journal Sentinel

Posted: Jan. 27, 2010

In a feat of biological alchemy, scientists at Stanford have turned the skin cells of a mouse into brain cells without ever taking the cells back to the embryonic state, raising hopes that medicine may be approaching a new era.

The work by scientists at Stanford University was described in a paper published online Wednesday in the journal Nature and builds on the 2007 discovery that human skin cells could be reprogrammed back to the embryonic state. The reprogramming of human cells was first accomplished by the labs of James Thomson at the University of Wisconsin-Madison and Shinya Yamanaka at Kyoto University in Japan.

"To me, this is huge progress for biomedical science," said Su-Chun Zhang, a UW stem cell researcher and professor of anatomy and neurology.

Full story.

New questions are being raised in stem-cell debate

by Carmen Leibel and Lisa Willemse

December 10, 2009 - (Edmonton) The University of Alberta's Timothy Caulfield is questioning some of the ethical and legal barriers facing a new stem cell procedure.

It was two years ago when a groundbreaking discovery turned ordinary skin cells back into an embryonic or "pluripotent" state. This was recognized as the solution to the controversial ethical question that has plagued stem-cell science for the past decade.

But is it the solution? Or have iPS cells (induced pluripotent stem cells) added a new dimension to the legal, social and ethical debates that are an important and necessary part of stem-cell advances?

Caulfield, research director at the U of A's Health Law Institute and principal investigator at the Stem Cell Network, says that while iPS technology eliminates some of the ethical issues specific to embryonic stem-cell research it also adds new challenges.

"From a legal perspective, iPS technology is fascinating and complex. For example, if an iPS cell can be made into a functional human gamete, the potential exists for reproductive purposes. What would this mean for donor consent, concerns about cloning and rights of a potential child to know its parents," said Caulfield.

Full story.

New skin stem cells surprisingly similar to those found in embryos

Scientists have discovered a new type of stem cell in the skin that acts surprisingly like certain stem cells found in embryos: both can generate fat, bone, cartilage, and even nerve cells. These newly-described dermal stem cells may one day prove useful for treating neurological disorders and persistent wounds, such as diabetic ulcers, says Freda Miller, an HHMI international research scholar.

Miller and her colleagues first saw the cells several years ago in both rodents and people, but only now confirmed that the cells are stem cells. Like other stem cells, these cell scan self-renew and, under the right conditions, they can grow into the cell types that constitute the skin's dermal layer, which lies under the surface epidermal layer. "We showed that these cells are, in fact, the real thing," says Miller, a professor at the University of Toronto and a senior scientist in the department of developmental biology at the Hospital for Sick Children in Toronto. The dermal stem cells also appear to help form the basis for hair growth.The new work was published December 4, 2009, in the journal Cell Stem Cell.

Full story.