US Scientists First Ever To Genetically Modify Human Embryos – Chronicle Day

The United States seems to be in the running when it comes to the experiments with human DNA. However, the subject s still very much covered with a veil of secrets and questions we have no answers to.

It looks like that the MIT Technology Review published a news report last week concerning the experiments in which the aim was to create genetically modified human embryos. This research was led by Shoukhrat Mitalipov, director of the Oregon Health & Science Universitys Center for Embryonic Cell and Gene Therapy, but neither he or his unversity wanted to make any statements concerning the research.

The university press office did, however, release a statement which said: Results of the peer-reviewed study are expected to be published soon in a scientific journal. No further information will be provided before then. It is pretty clear that there will be no way to get the extra details on the research before the study is published in the journal as to avoid any speculation and possible issues.

Mitalipov has also refused to comment any of the questions or statements released, including the report that was published. He has also not confirmed not negated that he has seen the report.

In 2013 Mitalipov and his research team had their first breakthrough when they cloned human stem cells and reprogrammed them to go back to their embryonic state. In 2007, they have announced that they made a clone of monkey embryo and managed to extract the cells from it.

Although it is not certain, and at this time cannot be confirmed, it is suspected that the genes targeted in this particular research are the ones associated with inherited diseases. Arthur Caplan, a professor and founder of the division of bioethics at New York University Langone Medical Center, who was not involved in the research commented: Im not surprised that they were looking at genetic diseases to try and see if they could target them, because thats exactly where I think the future inevitably leads.

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US Scientists First Ever To Genetically Modify Human Embryos - Chronicle Day

Controversial milestone: Scientists genetically modify human embryos for first time, reports say – The San Diego Union-Tribune

A team of researchers that includes a scientist from the Salk Institute in La Jolla has created the first genetically modified human embryos, the MIT Technology Review reported this week.

If the achievement is true the scientists in question have neither confirmed nor disputed the account it could mark a milestone in preventing transmission of genetic diseases instead of just treating them.

It would also rev up debate about the safety and ethics of genetically changing human beings, including what laws exist to safeguard patients and what constitutes a medically legitimate genetic modification.

The technology could be used to alter people for nonmedical purposes such as making them taller, giving them a specific eye shape or switching out their black hair for a shade of blonde decisions that could be seen as fundamentally upending the definition of human nature.

The Technology Review story said the scientists harnessed the gene-editing method called CRISPR, a milestone in its own right, to modify one-celled embryos and allow them to develop for a few days. Other news organizations have published their own articles about this purported accomplishment, including the well-respected biomedical website Stat.

Prominent biologist Shoukhrat Mitalipov of Oregon Health & Science University was the lead researcher on the study, according to the Technology Review and Stat stories. Both reports said he declined to comment.

Results of the peer-reviewed study are expected to be published soon in a scientific journal, Oregon Health & Science spokesman Erik Robinson said Thursday. He declined to specify what the study discovered.

The Technology Review story also said Jun Wu of the Salk Institute for Biological Studies took part in the research. On Thursday, the institute declined to discuss the study.

Mitalipov gained fame in 2013 for spearheading development of the first human embryonic stem cells genetically matched to specific living individuals. The method he and some colleagues employed, called somatic cell nuclear transfer, was originally used two decades ago to create Dolly the cloned sheep.

Those researchers had taken a nucleus from a donor cell in a sheep and transferred it into a sheep egg cell that had had its own nucleus removed. The combination cell acted like a normal fertilized egg, producing Dolly. That sheep had the DNA of the donor cell, so it was a nearly exact clone of the sheep where the donor cell was taken from.

Growing a creature in this way is called reproductive cloning, and the U.S. government bans such procedures on people. Mitalipov and colleagues performed what is called therapeutic cloning: They used the process to cultivate human embryonic stem cells, which are likewise genetically matched to the donor nucleus.

In theory, these stem cells could be grown into replacement tissues to repair disease or injury in the person with the matching DNA. Genetically matching the stem cells to a particular patient lowers the risk that tissue transplants would be rejected by the persons immune system.

Wu and other Salk researchers in the lab of Juan Carlos Izpisa Belmonte have collaborated with Mitalipov to explore somatic cell nuclear transfer as a therapy for mitochondrial diseases. Mitochondria are organelles that make most of the energy cells use and perform other vital functions. They carry their own DNA.

The scientists generated human stem cells in the lab, repaired mitochondrial defects and found that they were able to restore certain desired functions in cells.

They took human skin cells and inserted their nuclei into human egg cells with healthy mitochondria that had their own nuclei removed. Those manipulated egg cells were then grown until they produced embryonic stem cells, free of the defective mitochondria.

The United Kingdom has approved a method that resembles reproductive cloning to prevent inheritance of mitochondrial diseases. This process involves replacing the nucleus of an egg cell from a donor with healthy mitochondria with that from the egg cell of the mother-to-be with diseased mitochondria.

Whether the reports this week about genetically modified human embryos are true, the capability of genetically engineering human embryos is fast approaching, said a bioethicist and a stem cell researcher who have examined the issue.

But having the capability doesnt mean it should be done, said Michael Kalichman, co-founding director of the the Center for Ethics in Science and Technology at UC San Diego.

Kalichman said society isnt ready for genetically modifying humans, and that its time for the public to start paying attention to what has been considered a futuristic scientific issue.

The strongest argument for genetic modification is to stop diseases, he said. The strongest argument against the technology is that it might cause unanticipated problems.

Paul Knoepfler, a stem cell researcher at UC Davis, said no matter how much effort is spent to ensure patient safety, there are no guarantees.

The bottom line is that well never really know until someone tries it, Knoepfler said. Potential harm might not emerge until adulthood or even until the genetically altered people have their own children, he added.

The other big thing is, I am not really convinced we can draw a clear line between doing this for only medical purposes versus (cosmetic) traits, he said.

Finally, its not clear why genetically editing human embryos would even be needed to prevent transmission of a genetic disease, Knoepfler said.

We already have an existing technology which is basically embryo screening, he said. Multiple embryos can be generated through in vitro fertilization to find one that doesnt have the disease.

That would be much safer than actually doing an edit, he said.

Stem cells could treat mitochondrial disease

Oregon scientists make embryos with 2 women, 1 man

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Controversial milestone: Scientists genetically modify human embryos for first time, reports say - The San Diego Union-Tribune

3D printed brain-like tissue made from stem cells offers hope to address neurological disorders – Genetic Literacy Project

Scientists in Australia have used a 3D printer to create nerve cells found in the brain using a special bio-ink made from stem cells.

The research takes us a step closer to making replacement brain tissue derived from a patients own skin or blood cells to help treat conditions such as brain injury, Parkinsons disease, epilepsy and schizophrenia.

The bio-ink is made of human induced pluripotent stem cells (iPSC), which have the same power as embryonic stem cells to turn into any cell in the body, and possibly form replacement body tissues and even whole organs.

3D printing with bio-ink (ABC News)

[Jeremy Crookfrom the University of Wollongong stated]many neuropsychiatric disorders result from an imbalance of key chemicals called neurotransmittersFor example, he said, defective serotonin and GABA-producing nerve cells are implicated in schizophrenia and epilepsy[Thus] the team used 3D printing to make neurones involved in producing GABA and serotonin.

Apart from providing customized transplants, 3D printed tissue could be useful for medical research.

For example, tissue from a patient with epilepsy or schizophrenia could be created, specifically to study their particular version of the condition.

You can compare how neuronal networks form differently compared to healthy patient, said Dr Crook.

[Read the full study here]

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3D printed brain-like tissue made from stem cells offers hope to address neurological disorders - Genetic Literacy Project

Scientists create 3D-printed brain-like tissue from stem cells – ABC Online

Scientists in Australia have used a 3D printer to create nerve cells found in the brain using a special bio-ink made from stem cells.

The research takes us a step closer to making replacement brain tissue derived from a patient's own skin or blood cells to help treat conditions such as brain injury, Parkinson's disease, epilepsy and schizophrenia.

The bio-ink is made of human induced pluripotent stem cells (iPSC), which have the same power as embryonic stem cells to turn into any cell in the body, and possibly form replacement body tissues and even whole organs.

Jeremy Crook, who led the research, said the ability to customise brain tissue from a person's own body tissue was better for transplantation.

"That circumvents issues of immune rejection, which is common in organ transplantation," said Dr Crook, from the University of Wollongong and ARC Centre of Excellence for Electromaterials Science.

"It's personalised medicine."

Dr Crook said many neuropsychiatric disorders result from an imbalance of key chemicals called neurotransmitters, which are produced by specific nerve cells in the brain.

For example, he said, defective serotonin and GABA-producing nerve cells are implicated in schizophrenia and epilepsy while defective dopamine-producing cells are implicated in Parkinson's disease.

The team used 3D printing to make neurones involved in producing GABA and serotonin, as well as support cells called neuroglia, they reported in the journal Advanced Healthcare Material.

In the future, they plan to print neurones that produce dopamine.

"We might want to make a tissue that specifically generates that neurotransmitter for grafting into the brain of a Parkinson's patient," said Dr Crook.

"That's absolutely achievable."

To make the neurones, Dr Crook and colleagues used their bio-ink to print layers of a hatched pattern to create a 5 millimetre-sized cube.

They then "crosslinked" the cube into a firm jelly-like substance.

Growth factors and nutrients were then fed into the holes of this spongey "scaffold", encouraging the stem cells to grow and turn into neurons and support cells, linking up to form tissue.

Waste was also removed via the holes in the scaffold.

Dr Crook said once scaled up, blood vessels would be needed, but small transplants could be theoretically possible using the tissue developed so far.

Tissue engineer Makoto Nakamura from Toyama University in Japan said the study was "very impressive".

"This article indicates the good feasibility of 3D bioprinting with human iPS cells to engineer neural tissues," said Professor Nakamura, who recently wrote an overview on the use of 3D bioprinting in the journal Tissue Engineering.

But he said there were also risks with the technology.

A close up of the 'scaffold' made of 3D-printed induced pluripotent stem cells (iPSCs)

(Supplied: Gu et al/Advanced Healthcare Materials)

A close up of the 'scaffold' made of 3D-printed induced pluripotent stem cells (iPSCs)

Supplied: Gu et al/Advanced Healthcare Materials

One of the challenges of using iPSCs is that, like embryonic stem cells, they have the potential to develop into teratomas disturbing looking tumours that contain more than one type of tissue type (think toenails growing in brain tissue, or teeth growing in ovary tissue).

According to Professor Nakamura, it would be important to ensure all the stem cells had turned into nerve cells in the final transplanted material.

"Undesired tissue may grow if even only one immature [stem] cell contaminates [the tissue to be transplanted]," he said.

Dr Crook said the team was currently carrying out animal experiments to test if teratomas developed from the 3D printed nerve cells.

While this is a first step towards 3D printing of whole organs, Dr Crook said a whole functioning brain would be a much more complex task.

"That's a whole different scale. The tissue we print is uniform, and not made up of different regions like a brain," said Dr Crook.

Still, it is a goal the researchers are heading towards.

"We would like to get as close as possible to replicating the function of the brain on the bench," said research team member Professor Gordon Wallace.

Apart from providing customised transplants, 3D printed tissue could be useful for medical research.

For example, tissue from a patient with epilepsy or schizophrenia could be created, specifically to study their particular version of the condition.

"You can compare how neuronal networks form differently compared to healthy patient," said Dr Crook.

And the tissue could also be used to screen for effective drugs or electrical stimulation treatments.

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Scientists create 3D-printed brain-like tissue from stem cells - ABC Online

Stem cell research: the debate continues to rage – CosmicNovo.com (Science and Technology)

The list of medical or scientific endeavours mired in controversy is fairly short, but stem cell research and related therapy are some of the most contentious issues in modern science. Simply, stem cell therapy involves the use of stem cells to treat or prevent a disease or condition, a form of this type of treatment involves bone marrow transplant which is a relatively common operation. Whilst this may not strike you as something worthy of debate, it is because it is the further research in stem cell therapy that has become a battleground of ideology and discussion.

There is research and case studies showing that stem cell therapy involving cells from the umbilical cord blood of infants as well embryonic stem cells from human embryos. Although the former is fairly innocuous, is the latter, which requires a human embryo that has caused controversy, as to harvest them, you must destroy the embryo.

Understandably, there is a lot of opposition to the use of human embryonic stem cells in research, often times based on a range of philosophical, moral, or religious objections, with most protesters worried of cloning embryos just to harvest these cells. Theology, philosophy and morality aside, the medical possibilities of embryonic stem cells are almost limitless.

Doctors have explained that due to the nature of these cells, they are more flexible and can be put to a far greater range of uses than other more conventional stem cells. They pertain that these cells could help treat an incredibly high amount of diseases and illnesses including but not limited to neurodegenerative diseases and conditions such as diabetes and heart disease.

Of course, this only adds to the mounting debate surrounding the use of these cells, further driving questions from a moral and philosophical viewpoint as to whether or not it is ethical to be using embryonic stem cells, despite the purported benefits. Although research continues into the use of these specific cells, and governments grapple with potential legal and medical ramifications, it is important to realize that there are several other stem cell opportunities that do not require the same controversial source.

Although there has been blowback on other forms of research in the sector namely the use of umbilical blood the use of bone marrow transplants and other such alternative continue to save lives daily. However, until society catches up with science and medicine, there will be a continued debate as to the ethics and morality of this type of research, its applications, and what it could open the door for.

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Stem cell research: the debate continues to rage - CosmicNovo.com (Science and Technology)

Vatican’s Academy for Life Appoints Eugenicist – Church Militant

VATICAN CITY (ChurchMilitant.com) - The Pontifical Academy for Life (PAL) has added to its scandal by appointing a eugenicist involved in stem-cell research to its corp of 45 ordinary members, along with a pro-abortion philosopher, another pro-abortion eugenicist and a pro-contraception priest, who also supports euthanasia by starvation.

Professor Katarina Le Blanc, professor of stem cell research at the pro-abortion Swedish Karolinska Institute was appointed last month to PAL under Abp. Paglia. Le Blanc carries out her research, using stem cells derived from aborted babies even though the same academy, under the watch of Pope St. John Paul II, condemned such work in 2000.

In condemning the practice of experimenting on embryonic stem cells, PALremarked, "[It] is not hard to see the seriousness and gravity of the ethical problem posed by ... the production and/or use of human embryos."

There are other appointees to PAL with serious moral issues such as Fr. Maurizio Chiodi, who's supposedly a leading Italian moral theologian. He not only rejectsthe Church's ban on the use of artificial birth control but also believes it isn't obligatory to provide food and water to patients. Contrary to Fr. Chiodi's position, PAL stated in 2000 that food and water must always be provided to patients.

Nigel Biggar, one of 45 new ordinary members chosen to serve a five-year term on the Vatican's pro-life academy, believes it's morally acceptable to abort a person before 18 weeks of gestation. During an interview in 2011,Nigel, an Anglican minister and Regius Professor of Moral and Pastoral Theology at the U.K.'s University of Oxford, stated, "I would be inclined to draw the line for abortion at 18 weeks after conception, which is roughly about the earliest time when there is some evidence of brain activity and therefore of consciousness."

In spite of the fact that many of these appointments to the supposedly pro-life institute are manifestly not pro-life, the head of the institute, Abp. Paglia,defends the appointments.

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Vatican's Academy for Life Appoints Eugenicist - Church Militant

UW-Madison scientists grow functional artery cells from stem cells – Madison.com

In a step toward one of stem cell sciences chief goals, UW-Madison researchers have grown functional human artery cells that helped lab mice survive heart attacks.

The development, from the lab of stem cell pioneer James Thomson, could help scientists create arteries to use in bypass surgeries for cardiovascular disease, the nations top killer. Several challenges remain, however, and studies in people are years away.

This work provides valuable proof that we can eventually get a reliable source for functional arterial endothelial cells and make arteries that perform and behave like the real thing, Thomson said in a statement.

The research, reported Monday in the journal Proceedings of the National Academy of Sciences, is part of a federally funded effort at UW-Madison to create artery banks for cardiovascular surgery from universally compatible donors.

In a related project, other UW-Madison researchers are testing three-dimensional heart patches of heart muscle cells, grown from stem cells, in pigs. The goal is to replace diseased or damaged heart tissue in humans.

Since Thomson became the first scientist to successfully grow human embryonic stem cells in a lab in 1998, researchers around the world have been coaxing the universal cells into various cell types heart, pancreas, kidney, brain to develop therapies and better understand diseases.

Today, many researchers use cells reprogrammed to their embryonic state from mature cells known as induced pluri- potent stem, or iPS, cells as the raw material. Thomson helped discover iPS cells in 2007.

Many labs can convert embryonic stem cells or iPS cells into specific cell types, but developing specialized cell lines that are pure, functional and robust has been a challenge.

Thomson and his team set out to find a recipe for growing artery cells that would really function like arteries.

The researchers used two new techniques: single-cell RNA sequencing to identify genes highly expressed in cells that initiate artery development, and CRISPR-Cas9 gene editing to evaluate the function of the genes.

They found that five small molecules and growth factors are needed to encourage iPS cells to become functional artery cells. To their surprise, they discovered that insulin, a common growth factor that had been used before in trying to grow artery cells, actually inhibits such growth.

They used their recipe to make artery cells, and tested the cells in mice that had their left coronary arteries tied off to mimic heart attacks. Four weeks later, 83 percent of mice treated with the cells were alive, compared to 33 percent of mice that didnt get the cells.

We can use those cells to further create tissue-engineered arteries for bypass surgeries, said Jue Zhang, a scientist in Thomsons lab at the Morgridge Institute for Research and lead author of the study.

Developing off-the-shelf bypasses for surgery is the goal of an $8 million, seven-year grant UW-Madison received last year from the National Heart, Lung and Blood Institute to create universal artery banks.

The blood vessels of many cardiovascular disease patients arent suitable for use as bypasses, doctors say, and growing bypasses from individual patients stem cells would be timely and expensive. The hope is to use iPS cells from a rare population of genetically compatible donors to grow arteries anyone could use.

UW-Madison scientists, including engineers Tom Turng and Naomi Chesler and pathologist Igor Slukvin at the Wisconsin National Primate Research Center, plan to grow artery cells on scaffolds and test them in monkeys. If successful, the cells would be produced for human studies at the Waisman Biomanufacturing facility on campus.

The heart patches involve another $8.6 million, seven-year National Institutes of Health grant, shared with the University of Alabama-Birmingham and Duke University.

The patches involve three types of heart cells, derived from iPS cells, said Dr. Tim Kamp, a UW-Madison cardiologist and co-director of the universitys Stem Cell and Regenerative Medicine Center.

In studies in pigs, getting the patches to connect and survive when transplanted to pig hearts after heart attacks remains a challenge, Kamp said. Immune tolerance of the human grafts in pigs is another concern, he said.

But if such hurdles can be overcome, tests in humans could follow.

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GEN Roundup: Top Trends in Tissue Engineering – Genetic Engineering & Biotechnology News

References

1. F.T. Moutos et al., Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing, Proc. Natl. Acad. Sci. U.S.A. 113 (31) E4513E4522, doi: 10.1073/pnas.1601639113.

2. B. Zhang et al., Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis, Nat. Materials 15, 669678 (2016), doi:10.1038/nmat4570.

3. S. Shukla et al., Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1, Nat. Methods 14(5), 531-538 (May 2017),doi: 10.1038/nmeth.4258. Epub Apr 10, 2017.

4. M.M. Pakulska, S. Miersch, and M.S. Shoichet, Designer protein delivery: from natural occurring to engineered affinity controlled release systems, Science 351(6279):aac4750, doi: 10.1126/science.aac4750.

5. M.M. Pakulska, C.H. Tator, and M.S. Shoichet, Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1 promotes functional repair in the injured rat spinal cord, Biomaterials (accepted April 2017).

6. TissueGene, TissueGene to Highlight Invossa, the Worlds First Cell-Mediated Gene Therapy for Degenerative Osteoarthritis, at JP Morgan Healthcare Conference, Press Release,accessed June 12, 2017.

7. O.J.L. Rackham et al., A predictive computational framework for direct reprogramming between human cell types, Nat. Genetics 48, 331335 (2016), doi:10.1038/ng.3487.

8. D.B. Kolesky et al., Three-dimensional bioprinting of thick vascularized tissue, Proc. Natl. Acad. Sci. U.S.A. 113 (12), 31793184, doi: 10.1073/pnas.1521342113.

9. M.M. Laronda et al., A Bioprosthetic Ovary Created Using 3D Printed Microporous Scaffolds Restores Ovarian Function in Sterilized Mice, Nat. Commun. 8, 15261 (May 16, 2017).

10. I. Sagi et al., Derivation and differentiation of haploid human embryonic stem cells, Nature 532, 107111 (April 7, 2016), doi:10.1038/nature17408.

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GEN Roundup: Top Trends in Tissue Engineering - Genetic Engineering & Biotechnology News

Hurray for Gurdon and Yamanaka, Nobel Prize Winners for Pro-life Medicine – Gilmer Mirror

The research studies carried out by John B. Gurdon (Anglo-Saxon) and Shinya Yamanaka (Japanese) were awarded the Nobel Prize in Medicine. These two scientists are considered of being the fathers of cellular reprogramming. They have achieved to create cells that behave identically to embryonic cells, however, without having to destroy human embryos. The Swiss Academy declared that both Gurdon and Yamanaka have revolutionized the current knowledge of how cells and organisms are developed, which has led to the perfection of the absurd methods of diagnosis and therapy.

Jhon Bertrand Gurdon, professor of the Zoology Department of the University of Cambridge, admitted of feeling extremely honored for such a spectacular privilege.

Moreover, Shinya Yamanaka discovered the so called induced pluripotent stem cells (iPS), which have the same proprieties of the embryonic ones and are able to turn into whatever other type of body cell. He asserted that he will continue to conduct research in order to contribute to society and medicine. For him that is a duty.

Yamanaka created four types of genes that supply cells with their pluripotentiality, in other words, the same capacity that embryonic stem cells have. If implanted in differentiated cells, for example of skin, they become pluripotent stem cells. The iPS supply a vast amount of plasticity just as embryonic stem cells do, however, without requiring the extermination or cloning of human embryos, since the initial cells can be obtained from the same patient. In this aspect, these cells have the same status as adult stem cells do, with the advantage of their versatility.

The dilema that has been stirred by the iPS is being resolved due to recent studies carried out by Leisuke Kaji (Universidad de Edimburgo) and Andreas Nagy (Samuel Lunenfeld Research Institute of Mount Sinai Hospital of Toronto).

The created iPS perennially retain their pluripotentiality. There is still the need of research to be conducted concerning the control of the difference between these cells in order for them to create the tissue that is necessary for each case. As Kaji affirms in The Guardian, it is a step towards the practical use of reprogrammed cells in the field of medicine, which could eventually lead to eliminating the need of counting on human embryos as the main source of stem cells.

The Episcopal Subcommittee for the Family and Defense of Life of the Episcopal Conference, beliefs that no Catholic could support practices such as abortion, euthanasia or the production, freezing and/or manipulation of human embryos.

Clement Ferrer

Independent Forum of Opinion

http://indeforum.wordpress.com/

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Hurray for Gurdon and Yamanaka, Nobel Prize Winners for Pro-life Medicine - Gilmer Mirror

What makes stem cells into perfect allrounders – Phys.org – Phys.Org

June 27, 2017 Just a few days old embryonic cell clusters: with functional Pramel7 (left), without the protein (right) the development of the stem cells remains stuck and the embyos die. Credit: Paolo Cinelli, USZ

Researchers from the University of Zurich and the University Hospital Zurich have discovered the protein that enables natural embryonic stem cells to form all body cells. In the case of embryonic stem cells maintained in cell cultures, this allrounder potential is limited. Scientists want to use this knowledge to treat large bone fractures with stem cells.

Stem cells are considered biological allrounders because they have the potential to develop into the various body cell types. For the majority of stem cells, however, this designation is too far-reaching. Adult stem cells, for example, can replace cells in their own tissue in case of injury, but a fat stem cell will never generate a nerve or liver cell. Scientists therefore distinguish between multipotent adult stem cells and the actual allrounders - the pluripotent embryonic stem cells.

Epigenetic marks determine potential for development

Differences exist even among the true allrounders, however. Embryonic stem cells that grow in laboratory cell cultures are in a different state than the pluripotent cells found inside the embryos in the first days of development. In a study in the journal Nature Cell Biology, researchers led by Paolo Cinelli of the University Hospital Zurich and Raffaella Santoro of the University of Zurich have now demonstrated the mechanism by which natural allrounders differ from embryonic stem cells in cultures.

At the center of their discovery is a protein called Pramel7 (for "preferentially expressed antigen in melanoma"-like 7) found in the cells of embryonic cell clusters that are just a few days old. This protein guarantees that the genetic material is freed from epigenetic marks consisting of chemical DNA tags in the form of methyl groups. "The more methyl groups are removed, the more open the Book of Life becomes," Cinelli says. Since any cell of the human body can develop from an embryonic stem cell, all genes have to be freely accessible at the beginning. The more a cell develops or differentiates, the stronger its genetic material is methylated and "sealed closed" again. In a bone cell, for example, only those genes are active that the cell requires for its function, the biochemist explains.

Protein is responsible for perfect pluripotency

Despite its short action period of just a few days, Pramel7 seems to play a vital role: When the researchers headed up by Cinelli and Santoro switched off the gene for this protein using genetic tricks, development remained stuck in the embryonic cell cluster stage. In the cultivated stem cells, on the other hand, Pramel7 is rarely found. This circumstance could also explain why the genetic material of these cells contains more methyl groups than that of natural embryonic cells - the perfect allrounders, as Cinelli calls them.

Using the stem cell function to regenerate bone tissue

His interest in stem cells lies in the hope of one day being able to help people with complex bone fractures. "Bones are great at regenerating and they are the only tissue that does not build scars," Paolo Cinelli says. The bone stumps must be touching, however, in order to grow together. When a bone breaks in multiple places and even through the skin, for example, in a motorcycle accident, the sections of bone in between are often no longer usable. For such cases, a bone replacement is required. His team is studying carrier materials that they want to populate with the body's own stem cells in the future. "For this reason, we have to know how stem cells work," Cinelli adds.

Explore further: New tools to study the origin of embryonic stem cells

More information: Urs Graf et al, Pramel7 mediates ground-state pluripotency through proteasomalepigenetic combined pathways, Nature Cell Biology (2017). DOI: 10.1038/ncb3554

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