Novel method to make safer human stem cells uses just one gene

London, Aug 29 (ANI): Inching closer to curing diseases like Parkinson’s using cells generated from a patient’s own body, researchers have successfully reprogrammed human nerve cells back to an embryo-like state by using just a single gene.

It is known that embryonic stem cells are pluripotent – they can develop into any of the body’s cell types.

But such cells are not available in large numbers, as they can only be harvested from a donated egg or embryo, and, for ethical reasons, most countries have laws restricting their use.

In 2006, Shinya Yamanaka and his colleagues at Kyoto University in Japan successfully made mouse cells pluripotent by reprogramming skin cells into a state like embryo cells.

They did so by using retroviruses to insert four genes – known as “factors” – into the cells’ DNA.

They repeated the trick a year later with human cells.

However, using genes and retroviruses in this way increases the risk of the cell becoming cancerous, not just because tinkering with DNA has that effect, but also because two of the four factors are known to cause cancer.

In a bid to make these promising cells in a safe way, Hans Scholer’s team at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, has been working to achieve pluripotency using fewer factors.

Last year, they did this with the two factors that do not cause cancer, and now they have simplified the recipe further, doing it with just one.

“Remarkably, it turns out that three of these four essential factors are already expressed in human neural stem cells – although not in skin cells – so we only needed to add one factor, OCT4,” New Scientist quoted Boris Greber, a member of the team, as saying.

He said that the cells from neural tissue are much easier to reprogram than skin cells, and are less prone to mutations.

It is much harder to get a sample of neural stem cells than skin cells, as it can be done via extracting the cells from the dental pulp of teeth, said Greber.

Inserting even one gene into the chromosome of a cell still permanently modifies its DNA, which is why the new method will remain a lab tool instead of being allowed in the clinic.

However, the researchers are hoping that it will help them improve methods for producing embryonic stem cells.

“Ideally, we will be able to find a chemical that does the same job of expressing the factor without the need for a gene,” said Greber.

Earlier this year, researchers in California managed just that when they reprogrammed mouse fibroblasts using a cocktail of proteins.

That technique did not involve inserting genes, and, thus, shouldn’t raise the cancer risk. But that was far less efficient.

“Without stable intervention using viruses, the frequency of reprogramming goes down and you have to wait a long time. We don’t have the perfect method yet,” said Greber.

The study has been published in the journal Nature. (ANI)

Scientists create artificial sperm cells from human embryonic stem cells

London, July 8 (ANI): Scientists have achieved a major breakthrough in making sperm-like cells from human embryonic stem cells.

Karim Nayernia, of the University of Newcastle Upon Tyne in the UK, has revealed that these cells can swim like sperm do.

He says that his team used the same technique to create sperm-like cells from human embryonic stem cells that he had used in 2006 to produced sperm from mouse embryonic stem cells.

The team labelled embryonic stem cells with a fluorescent marker attached to a particular gene that is expressed during reproductive-cell development, and cultured the cells in a medium that encourages differentiation into sperm cells.

The researchers observed that about three per cent of the resulting cells contained enough DNA for only one set of chromosomes, suggesting that meiosis had occurred.

Some of these cells also formed tails and were motile, they said.

Nayernia and his colleagues have yet to analyse methylation patterns in their sperm-like cells, or conduct a detailed study of the cells’ morphology.

While there work has been hailed by other scientists, the sperm-like cells created by the researchers will still require much more characterization before they can be used as an experimental model for the study of inherited diseases and infertility.

Another hurdle is that, in several countries, it may actually be illegal even if these cells were properly characterised.

Nayernia admits it, but still insists that his team’s work was a “proof-of-principle experiment”.

“We don’t claim that it is fully normal sperm, but they do have some of the right characteristics,” Nature magazine quoted him as saying.

Meanwhile, he and his colleagues have also launched a project to produce sperm cells from induced pluripotent stem cells, which can be generated from adult cells.

The researchers believe that such cells would make it easier to derive sperm cells from many individuals.

“Then we can, for example, see whether environmental factors or genetic factors are affecting fertility, and which step of sperm production has been affected by those factors,” he says. (ANI)

New way to reduce tumour-risk factor in stem cell therapy unveiled

Washington, May 7 (ANI): Paving the way for advancement in the field of stem cell therapy, scientists have discovered a method to potentially eliminate the tumour-risk factor in utilizing human embryonic stem cells.

Human embryonic stem cells are theoretically capable of differentiation to all cells of the mature human body, and are hence defined as “pluripotent”.

The above capability, along with the ability to remain undifferentiated indefinitely in culture, make regenerative medicine using human embryonic stem cells a potential tool for the treatment of various diseases, including diabetes, Parkinson’s disease and heart failure.

However, the biggest hurdle in using stem cells is their tendency to grow into a specific kind of tumour, called teratoma, when they are implanted in laboratory experiments into mice.

And scientists have thought that the tumorigenic feature will be manifested upon transplantation to human patients as well.

Thus the development of tumours from embryonic stem cells is especially puzzling, keeping in mind that these cells start out as completely normal cells.

So, researchers at the Stem Cell Unit in the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University analysed the genetic basis of tumour formation from human embryonic stem cells, and identified a key gene that is involved in this unique tumorigenicity.

The gene called survivin is expressed in most cancers and in early stage embryos, but it is almost completely absent from mature normal tissues.

The gene is especially highly expressed in undifferentiated human embryonic stem cells and in their derived tumours.

The researchers could neutralise the activity of survivin in the undifferentiated cells as well as in the tumours, and thus managed to initiate programmed cell death (apoptosis) in those cells.

The inhibition of this gene just before or after transplantation of the cells could minimize the chances of tumour formation.

But the researchers have warned that a combination of strategies may be needed to address the major safety concerns regarding tumour formation by human embryonic stem cells. (ANI)

Blood cells can be reprogrammed to act as embryonic stem cells

Washington, Apr 21 (ANI): Embryonic stem cells have long been coveted for their potential to treat a multitude of diseases. Now, researchers have successfully reprogrammed cells found in circulating blood into cells that are molecularly and functionally indistinguishable from embryonic stem cells.

The new study may provide a readily accessible source of stem cells and an alternative to harvesting embryonic stem cells.

“Our findings provide the first proof that cells from human blood can morph into stem cells,” said senior study author Dr George Q. Daley, an investigator for the Howard Hughes Medical Institute at Children’s Hospital, Boston.

“Making pluripotent stem cells from blood, which is one of the easiest tissues to obtain, provides an easy strategy for generating patient-specific stem cells that are valuable research tools and may one day be used to treat a number of diseases,” he added.

To produce the new stem cells called pluripotent (iPS), the researchers collected the blood from a 26-year-old male donor.

From the blood sample, they isolated CD34+ cells, a type of stem cell that produces only blood cells, and cultured them in growth factors for six days to increase their number.

During the culture, the scientists infected the CD34+ cells with viruses carrying reprogramming factors, genes normally expressed in embryonic stem cells that can reset the blood cells to an embryonic state.

Colonies of cells exhibiting physical characteristics similar to embryonic stem (ES) cells appeared about two weeks after the procedure.

In further studies, the iPS cells readily developed into clusters of cells called embryoid bodies from which cells of virtually any type can develop.

“Not only has this work identified a new programmable cell type, but the cells are easy to obtain and analyze in many research laboratories and bone marrow transplantation centers around the world,” said Dr Grover C. Bagby, Professor of Medicine and Molecular and Medical Genetics at Oregon Health and Science University.

The study appears online in journal Blood. (ANI)

Novel stem cell therapy may treat deafness

Washington, Mar 29 (ANI): In a breakthrough study, researchers have developed a new stem cell therapy that may help in treating hearing impairment.

Deafness typically involves the loss of sensory receptors, called hair cells, for their “tufts” of hair-like protrusions, and their associated neurons.

Led by Dr. Marcelo N. Rivolta of the University of Sheffield, researchers have has successfully isolated human auditory stem cells from foetal cochleae (the auditory portion of the inner ear) and found that they could be differentiated into sensory hair cells and neurons.

The researchers carefully dissected and cultured cochlear cells from 9-11 week-old human fetuses.

They then expanded the cells and maintained in vitro for up to one year, with continued division for the first 7 to 8 months and up to 30 population doublings, which is similar to other non-embryonic stem cell populations, such as bone marrow.

Gene expression analysis showed that all cell lines expressed otic markers that lead to the development of the inner ear as well as markers expressed by pluripotent embryonic stem cells, from which all tissues and organs develop.

The researchers could formulate conditions that allowed for the progressive differentiation into neurons and hair cells with the same functional electrophysiological characteristics as cells seen in vivo.

“The results are the first in vitro renewable stem cell system derived from the human auditory organ and have the potential for a variety of applications, such as studying the development of human cochlear neurons and hair cells, as models for drug screening and helping to develop cell-based therapies for deafness,” said the authors.

Although the hair cell-like cells did not show the typical formation of a hair bundle, the authors suggest that future studies will aim to improve the differentiation system.

Now, the researchers are working on using the knowledge from this study to optimise the differentiation of human embryonic stem cells into ear cell types.

“Although considerable information has been obtained about the embryology of the ear using animal models, the lack of a human system has impaired the validation of such information,” noted the authors.

Dr Ralph Holme, director of biomedical research for Royal National Institute for Deaf and Hard of Hearing People, said: “There are currently no treatments to restore permanent hearing loss so this has the potential to make a difference to millions of deaf people.”

The study is published in the April issue of Stem Cells. (ANI)

Stem cell breakthrough may offer possible cures for diabetes, Parkinson’s disease

London, March 2 (ANI): Scientists have reached a step closer to developing potential treatments for devastating diseases including spinal cord injury, macular degeneration, diabetes and Parkinson’s disease, thanks to a new method of creating stem cells discovered by researchers at Mount Sinai Hospital in Canada.

The researchers say that their study accelerates stem cell technology, and provides a road map for new clinical approaches to regenerative medicine.

“We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable,” Nature magazine quoted Dr. Andras Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Investigator at the McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration, as saying.

“This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues such as a patient’s own skin cells,” the researcher added.

Dr. Nagy revealed that his method helps create pluripotent stem cells-which can develop into most other cell types-without disrupting healthy genes. The researcher added that the method involves a novel wrapping procedure to deliver specific genes to reprogram cells into stem cells.

Scientists have to date relied upon approaches that requite the use of viruses to deliver the required genes, a method that carries the risk of damaging the DNA.

Given that Dr. Nagy’s method does not require viruses, it overcomes a major hurdle for the future of safe, personalized stem cell therapies in humans.

“This research is a huge step forward on the path to new stem cell-based therapies and indicates that researchers at the Lunenfeld are at the leading edge of regenerative medicine,” said Dr. Jim Woodgett, Director of Research for the Samuel Lunenfeld Research Institute of Mount Sinai Hospital.

Regenerative medicine refers to enabling the human body to repair, replace, restore and regenerate its own damaged or diseased cells, tissues and organs. (ANI)

Skin cells may help mend your broken heart

Washington, February 13 (ANI): Having demonstrated in their previous studies that skin cells could be turned back into stem cells, University of Wisconsin-Madison scientists have now shown that such “induced” cells can actually form the specialized cells that make up heart muscle.

Reporting their findings in the journal Circulation Research, the researchers claimed that that they were able to grow working heart-muscle cells from induced pluripotent stem cells, known as iPS cells.

Tim Kamp, UW-Madison School of Medicine and Public Health professor of medicine, revealed that the heart cells were originally reprogrammed from human skin cells by his co-authors on the study, James Thomson and Junying Yu.

“It’s an encouraging result because it shows that those cells will be useful for research and may someday be useful in therapy. If you have a heart failure patient who is in dire straits – and there are never enough donor hearts for transplantation – we may be able to make heart cells from the patient’s skin cells, and use them to repair heart muscle. That’s pretty exciting,” said Kamp, who is also a cardiologist with UW Health.

The researchers used a virus to insert four transcription factors into the genes of the skin cell, reprogramming it back to an embryo-like state.

However, since the virus is taken up by the new cell, the researchers fear that it may eventually cause cancer.

Considering this, they suggest that therapies from reprogrammed skin cells will have to wait until new methods are perfected.

Kamp, however, still calls his team’s findings to be significant, saying that the speed at which knowledge is progressing is very encouraging.

His latest research, proving that iPS cells can become functional heart cells, is just one step along the way to better understanding and treatment of disease.

“We’re excited about it, because it’s the some of the first research to show it can be done, but in the future, we’ll probably say, ‘Well, of course it can be done.’ But you don’t know until you do it. It’s a very mysterious and complicated dance to get these cells to go from skin cells to stem cells to heart cells,” he says. (ANI)