From pluripotency to totipotency

While it is already possible to obtain in vitro pluripotent cells (ie, cells capable of generating all tissues of an embryo) from any cell type, researchers from Maria-Elena Torres-Padilla’s team have pushed the limits of science even further. They managed to obtain totipotent cells with the same characteristics as those of the earliest embryonic stages and with even more interesting properties. Obtained in collaboration with Juanma Vaquerizas from the Max Planck Institute for Molecular Biomedicine (Münster, Germany), these results are published on 3rd of August in the journal Nature Structural & Molecular Biology.

Just after fertilization, when the embryo is comprised of only 1 or 2 cells, cells are “totipotent“, that is to say, capable of producing an entire embryo as well as the placenta and umbilical cord that accompany it. During the subsequent rounds of cell division, cells rapidly lose this plasticity and become “pluripotent”. At the blastocyst stage (about thirty cells), the so-called “embryonic stem cells” can differentiate into any tissue, although they alone cannot give birth to a foetus anymore. Pluripotent cells then continue to specialise and form the various tissues of the body through a process called cellular differentiation.

For some years, it has been possible to re-programme differentiated cells into pluripotent ones, but not into totipotent cells. Now, the team of Maria-Elena Torres-Padilla has studied the characteristics of totipotent cells of the embryo and found factors capable of inducing a totipotent-like state.

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Programming adult stem cells to treat muscular dystrophy and more by mimicking nature

"Inducing Stem Cell Myogenesis Using NanoScript" ACS Nano

Stem cells hold great potential for addressing a variety of conditions from spinal cord injuries to cancer, but they can be difficult to control. Scientists are now reporting in the journal ACS Nano a new way to mimic the body’s natural approach to programming these cells. Using this method, they successfully directed adult stem cells to turn specifically into muscle, which could potentially help treat patients with muscular dystrophy.

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Scientists stumble across unknown stem-cell type

‘Region-selective’ pluripotent cells raise possibility of growing human organs in animals.

Sara Reardon

06 May 2015

 A newly discovered type of stem cell could help provide a model for early human development — and, eventually, allow human organs to be grown in large animals such as pigs or cows for research or therapeutic purposes.

Juan Carlos Izpisua Belmonte, a developmental biologist at the Salk Institute for Biological Studies in La Jolla, California, and his colleagues stumbled across a previously unknown variety of pluripotent cell — which can give rise to any type of tissue — while attempting to graft human pluripotent stem cells into mouse embryos.

Scientists previously knew about two other types of pluripotent stem cells, but growing them in large numbers or guiding them to mature into specific types of adult cells has proven difficult. Writing in Nature, Izpisua Belmonte and his colleagues report a type of pluripotent cell that is easier to grow in vitro and grafts into an embryo when injected into the right spot. They call them region-selective pluripotent stem cells (rsPSCs).

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Stem cell advance yields mature heart muscle cells

by Renee Meiller

A team of University of Wisconsin-Madison researchers has induced human embryonic stem cells (hESC) to differentiate toward pure-population, mature heart muscle cells, or cardiomyocytes.

A substrate patterned with a precisely sized series of channels played a critical role in the advance.

Published online in the journal Biomaterials, the research could open the door to advances in areas that include tissue engineering and drug discovery and testing.

Researchers currently can differentiate hESC into immature heart muscle cells. Those cells, however, don't develop the robust internal structures — repeating sections of muscle cells called sarcomeres — that enable cardiomyocytes to produce the contracting force that allows the heart to pump blood. Other cell components that allow heart muscle cells to communicate and work together also are less developed in immature cardiomyocytes.

One barrier to efforts to produce more mature cells is the culture surface itself; hESC are notoriously finicky. "It's really hard to culture stem cells effectively and to provide them with an environment that's going to help them to thrive and differentiate in the way you want," says lead author Wendy Crone, a professor of engineering physics, biomedical engineering and materials science and engineering at UW-Madison.

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Steering stem cells with magnets

Quinn Eastman

July 16, 2013

Magnets could be a tool for directing stem cells’ healing powers to treat conditions such as heart disease or vascular disease.

By feeding stem cells tiny particles made of magnetized iron oxide, scientists at Emory and Georgia Tech can then use magnets to attract the cells to a particular location in a mouse's body after intravenous injection.

[...]

The type of cells used in the study, mesenchymal stem cells, are not embryonic stem cells. Mesenchymal stem cells can be readily obtained from adult tissues such as bone marrow or fat. They are capable of becoming bone, fat and cartilage cells, but not other types of cell such as muscle or brain. They secrete a variety of nourishing and anti-inflammatory factors, which could make them valuable tools for treating conditions such as cardiovascular disease or autoimmune disorders.

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Researchers create the inner ear from stem cells, opening potential for new treatments

July 10, 2013

Indiana University scientists have transformed mouse embryonic stem cells into key structures of the inner ear. The discovery provides new insights into the sensory organ's developmental process and sets the stage for laboratory models of disease, drug discovery and potential treatments for hearing loss and balance disorders.

A research team led by Eri Hashino, Ph.D., Ruth C. Holton Professor of Otolaryngology at Indiana University School of Medicine, reported that by using a three-dimensional cell culture method, they were able to coax stem cells to develop into inner-ear sensory epithelia—containing hair cells, supporting cells and neurons—that detect sound, head movements and gravity. The research was reportedly online Wednesday in the journal Nature.

Previous attempts to "grow" inner-ear hair cells in standard cell culture systems have worked poorly in part because necessary cues to develop hair bundles—a hallmark of sensory hair cells and a structure critically important for detecting auditory or vestibular signals—are lacking in the flat cell-culture dish. But, Dr. Hashino said, the team determined that the cells needed to be suspended as aggregates in a specialized culture medium, which provided an environment more like that found in the body during early development.

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Study Challenges Long-held Assumption of Gene Expression in Embryonic Stem Cells

July 3, 2013

CAMBRIDGE, Mass. – Whitehead Institute researchers have determined that the transcription factor Nanog, which plays a critical role in the self-renewal of embryonic stem cells, is expressed in a manner similar to other pluripotency markers. This finding contradicts the field’s presumptions about this important gene and its role in the differentiation of embryonic stem cells.

A large body of research has reported that Nanog is allelically regulated—that is, only one copy of the gene is expressed at any given time—and fluctuations in its expression are responsible for the differences seen in individual embryonic stem (ES) cells’ predilection to differentiate into more specialized cells. These studies relied on cells that had a genetic marker or reporter inserted in the DNA upstream of the Nanog gene. This latest research, published in this week’s edition of the journal Cell Stem Cell, suggests that results from studies based on this approach could be called into question.

To quantify the variations in Nanog expression, Dina Faddah, a graduate student in the lab of Whitehead Institute Founding Member Rudolf Jaenisch, looked at hundreds of individual mouse ES cells with reporters inserted immediately downstream of the Nanog gene. One Nanog allele had a green reporter, while the other had a red reporter, allowing Faddah to determine which of the two alleles was being expressed.

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Groups attack Wisconsin Alumni Foundation's embryonic stem cell patent

By Kathleen Gallagher of the Journal Sentinel

Two nonprofit groups are continuing their challenge to one of the Wisconsin Alumni Foundation's key embryonic stem cell patents by asking a federal appeals court to invalidate it.

The Public Patent Foundation, based in New York, and Consumer Watchdog, Santa Monica, Calif., filed a brief Tuesday with the U.S. Court of Appeals for the Federal Circuit. The Public Patent Foundation was one of the successful challengers in the recently decided case in which the Supreme Court ruled that genes cannot be patented.

"WARF's broad patent on all human embryonic stem cells is invalid for a number of reasons and we are confident the Court of Appeals will agree," said Dan Ravicher, the foundation's executive director. The groups believe that all researchers should have unfettered access to embryonic stem cells, which scientists believe could help treat many diseases.

A WARF spokeswoman declined to comment, saying the foundation needed to review the filing with its attorneys.

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Waisman scientists model human disease in stem cells

by David Tenenbaum

 

Many scientists use animals to model human diseases. Mice can be obese or display symptoms of Parkinson's disease. Rats get Alzheimer's and diabetes.

But animal models are seldom perfect, and so scientists are looking at a relatively new type of stem cell, called the induced pluripotent stem cell (iPS cell), that can be grown into specialized cells that become useful models for human disease.

IPS cells are usually produced by reprogramming a skin sample into a primitive form that is able to develop into all of the specialized cells in the body. In the laboratories at the Waisman Center at UW-Madison, scientists are growing iPS cells into models of disorders caused by defective nerve cells. The technology depends on work pioneered over the past decade or so by Su-Chun Zhang, a neuroscientist who leads the iPS Core at Waisman, which also produces cells for other investigators on campus.

The multidisciplinary Waisman Center, now in its 40th year, combines treatment with clinical and basic research to address many of the most complex and disabling disorders of development.

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CSIRO develops test to improve stem cell safety

The breakthrough is a significant step in improving the quality of iPS cells and identifying unwanted cells that can form tumours. The test also determines how stable iPS cells are when grown in the lab.

Dr Andrew Laslett and his team have spent the last five years working on the project. The research has focused on comparing different types of iPS cells with human embryonic stem cells. iPS cells are now the most commonly used pluripotent stem cell type for research.

"The test we have developed allows us to easily identify unsafe iPS cells. Ensuring the safety of these cell lines is paramount and we hope this test will become a routine screen as part of developing safe and effective iPS-based cell therapies," says Dr Laslett.

Using their test method, Dr Laslett's team has shown that certain ways of making iPS cells carry more risks. When the standard technique is used, which relies on viruses to permanently change the DNA of a cell, unwanted tumours are more likely to form. In comparison, cells made using methods which do not alter cell DNA, do not form tumours.

Dr Laslett hopes the study and the new test method will help to raise the awareness and importance of stem cell safety and lead to improvements in quality control globally.

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