Tag Archives: reprogramming

Mice created from skin cells

From Cox Newspapers

WEST PALM BEACH, Fla. — Scientists at The Scripps Research Institute in San Diego have created healthy adult mice out of mouse skin cells — no sperm, no egg. Just skin.

The feat, described in the scientific journal Nature this week, was intended to prove that adult cells can be reprogrammed backward in their development, until they have all the desirable characteristics of embryonic stem cells.

According to Gerard McGill, a medical ethicist at Duquesne University’s Center for Healthcare Ethics, this means the ability to treat diabetes, Alzheimer’s, Parkinson’s, hearing loss, or spinal cord damage with a patient’s own cells is within reach.

“It proves that reprogrammed cells are equivalent to embryonic stem cells,” McGill said. “Treatments are at least 15 or 20 years away, but they are reasonable.”

Reprogramming mouse skin cells to grow into complete mice required advances in mouse genetics, genetic engineering, stem cell biology and reproductive technology.

The scientists started using standard fetal mouse skin cells. They then genetically engineered viruses to carry genes for four key proteins believed to be able to reprogram a cell’s behavior. The viruses infected the skin cells, forcing them to produce the compounds.

The scientists hand-selected cells that had the most obvious stem-cell-like traits.

The cells were eventually transferred into fertile female mice.

Two of the embryos survived to become fertile adults.

Scientists Reprogram Clearly Defined Adult Cells Into Pluripotent Stem Cells — Directly And Without Viruses

From ScienceDaily.com

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Scientists Find Differences in Embryonic Stem Cells and Reprogrammed Skin Cells

From Newswise.com

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 Bill 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, 2009 issue of the journal Cell Stem Cell.

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UW researchers find safer way to reprogram cells

By Mark Johnson of the Journal Sentinel

Having mastered the ability to roll back a cell’s clock to its embryonic origin, scientists at the University of Wisconsin-Madison cleared a major technical hurdle this week, raising hopes that the technique could usher in a new kind of medicine that exploits the body’s own repair system.

Stem cell pioneer James Thomson and his colleagues reported Thursday that they have developed a safer way of turning cells from the foreskins of newborns into something very similar to embryonic stem cells.

Previous methods accomplished the trick but left behind viruses and outside genes, remnants of which could cause mutations, block the cells from growing into more specific types and even lead to tumors.

The UW team bypassed this obstacle by delivering the special genes with a plasmid, a small, very stable circle of DNA. This package reprogrammed the skin cells and was eventually diluted out of them. What remained were cells that appear to have the healing potential of embryonic stem cells, Thomson and his colleagues reported in the journal Science.

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Scientists Create Monkey Stem Cells

(Ivanhoe Newswire) — The successful creation of the first induced pluripotent stem (iPS) cell line from adult monkey skin may have important implications for direct reprogramming capabilities across different species.

Previous studies have shown that induction of four key transcription factors can reprogram adult mouse and human skin cells into iPS cells. Until now, iPS cell creation had not been demonstrated in any other species.

Researchers at Peking University in Beijing, China retrofit viruses to express the four key factors to infect adult monkey skin cells. This technique led to the creation of cells that displayed multiple hallmarks of embryonic stem cells. These cells possessed the ability to develop into multiple types of differentiated cells.

These findings could potentially be useful for the creation of clinically valuable primate models for human disease. The direct reprogramming model may also be a universal strategy for generating iPS cells in other species.

SOURCE: Cell Stem Cell, 2008;3:587-590

Wisconsin team starts with skin, derives liver cells

By Mark Johnson of the Journal Sentinel, JSOnline.com

Just after 5 p.m. doors rattle shut and feet begin to shuffle past the narrow lab where Karim Si-Tayeb sits hunched over a microscope, all but invisible to the scientists leaving the Medical College of Wisconsin.

Si-Tayeb has already worked eight hours and will work five more, eyes locked on the living cells in his care. Under the microscope, their tiny colonies resemble constellations of tightly packed stars. They carry his ambition.

“A few months ago I was working and it struck me how incredibly cool this is,” he said, sliding a dish of unusual cells under the microscope, cells he had scientifically altered. “This revolution is occurring, and you are part of it.”

Early this year the 32-year-old postdoctoral student from France joined a biomedical revolution by reprogramming human skin cells back to their embryonic origin, just as James Thomson in Madison and Shinya Yamanaka in Japan did when they made headlines in November 2007. Now Si-Tayeb and his supervisor, Stephen A. Duncan, a Medical College professor, were engaged in the next great race.

In 2008, scientists began trying to turn the new reprogrammed cells into all of the building blocks doctors might use to treat a multitude of diseases. Cardiac cells to repair a damaged heart. Insulin-producing cells to help diabetics. Photoreceptor cells to restore lost vision.

The work would be crucial if stem cells were to fulfill their promise and begin a new wave of medicine.

Duncan and Si-Tayeb were tryingto become the first scientists to use the new technology to make liver cells. They hoped the liver cells would someday help patients with a relatively rare form of inherited diabetes called MODY (mature onset diabetes of the young). Reprogrammed cells from MODY patients could provide a microscopic view of the disease as it progresses and give scientists a target for drug testing.

The stakes were high for Si-Tayeb, still early in his career and dreaming of a big scientific paper with his name on it.

At night, Duncan lay awake worrying. When he did drift off to sleep, sometimes he dreamed of work, the anxiety flowing through him, waking him with a jolt. What if their analysis was flawed? What if while they worried and double-checked, another scientist published the same discovery? As much as he wanted to be first, Duncan vowed no corners would be cut.

“Rigor in science is everything,” he said. “Without it you have nothing.”

Their dilemma was now the dilemma of many in the field, an illustration of how a major advance alters the scientific landscape.

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Patient-derived induced stem cells retain disease traits

From Genengnews.com

When neurons started dying in Clive Svendsen’s lab dishes, he couldn’t have been more pleased.

The dying cells the same type lost in patients with the devastating neurological disease spinal muscular atrophy confirmed that the University of Wisconsin-Madison stem cell biologist had recreated the hallmarks of a genetic disorder in the lab, using stem cells derived from a patient. By allowing scientists the unparalleled opportunity to watch the course of a disease unfold in a lab dish, the work marks an enormous step forward in being able to study and develop new therapies for genetic diseases.

As reported this week in the journal Nature, Svendsen and colleagues at UW-Madison and the University of Missouri-Columbia created disease-specific stem cells by genetically reprogramming skin cells from a patient with spinal muscular atrophy, or SMA. In this inherited disease, the most common genetic cause of infant mortality, a mutation leads to the death of the nerves that control skeletal muscles, causing muscle weakness, paralysis, and ultimately death, usually by age two.

Genetic reprogramming of skin cells, first reported in late 2007 by UW-Madison stem cell biologists James Thomson and Junying Yu and a Japanese group led by Shinya Yamanaka, turns back the cells’ developmental clock and returns them to an embryonic-like state from which they can become any of the body’s 220 different cell types. The resulting induced pluripotent stem cells, known as iPS cells, harness the blank-slate developmental potential of embryonic stem cells without the embryo and have been heralded as a powerful potential way to study development and disease.

Just one year later, the new work is fulfilling that promise.

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Caption: The nerves that control muscles, known as motor neurons (shown here in red), are lost in the devastating genetic disease called spinal muscular atrophy, causing weakness, paralysis, and early death. A team of UW-Madison stem cell biologists recreated the hallmarks of this disease in the lab using genetically reprogrammed stem cells created from a young SMA patient’s skin. The work gives scientists the opportunity to study the full progression of a disease in the lab and should improve understanding and treatment of genetic disorders. The motor neurons shown here were grown from cells from the patient’s healthy mother.
Photo: provided by Clive Svendsen, cnsvendsen@wisc.edu