Jazz Pharma Begins Rolling NDA For Defibrotide In Hepatic VOD

By Estel Grace Masangkay

Jazz Pharmaceuticals announced that it has started the rolling submission of a New Drug Application (NDA) for defibrotide as treatment for severe hepatic veno-occlusive disease (VOD) in patients undergoing hematopoietic stem-cell transplantation (HSCT) therapy.

Defibrotide is approved and indicated in the EU as treatment for severe hepatic VOD in patients one month old and above undergoing HSCT therapy. The drug has also received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of VOD. The company announced earlier this year that it will acquire rights to defibrotide from Sigma-Tau Pharmaceuticals through Jazzs subsidiary Gentium.

Veno-occlusive disease is an early complication in patients under HSCT therapy. The therapy is performed to treat hematological malignancies, certain tumors, and other non-malignant disorders. Severe VOD can be deadly and is linked with multi-organ failure. The condition is fatal in 80 percent of patients.

Jazz presented analysis of positive results from a Phase 3 trial of defibrotide in severe hepatic VOD at the recent American Society of Hematology (ASH) 56th Annual Meeting and Exposition held in San Francisco, California.

Jeffrey Tobias, EVP and CMO of Jazz Pharmaceuticals, said, We expect to complete the submission of the NDA in the first half of 2015, at which time we will be requesting a Priority Review of the application, and we will continue to work closely with the FDA as we seek approval of the NDA. We will continue to provide patients access to defibrotide through an expanded access treatment protocol that is open under an ongoing investigational new drug application in the U.S.

The FDAs Fast Track designation enables faster development and review of drugs that treat serious, deadly conditions and that address significant unmet medical needs. The Fast Track rolling submission process permits a company to submit parts of its New Drug Application (NDA) for review as soon as they are completed instead of waiting until all sections of the application are available before submitting them as a whole.

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Jazz Pharma Begins Rolling NDA For Defibrotide In Hepatic VOD

Baby cells learn to communicate using the lsd1 gene

21 hours ago Fruit fly ovarian follicle progenitor cells, with different colors marking a specific kind of activity (red) specific gene expression (green) and nuclear DNA (blue). Credit: Ming-Chia Lee and Allan Spradling

We would not expect a baby to join a team or participate in social situations that require sophisticated communication. Yet, most developmental biologists have assumed that young cells, only recently born from stem cells and known as "progenitors," are already competent at inter-communication with other cells.

New research from Carnegie's Allan Spradling and postdoctoral fellow Ming-Chia Lee shows that infant cells have to go through a developmental process that involves specific genes before they can take part in the group interactions that underlie normal cellular development and keep our tissues functioning smoothly. The existence of a childhood state where cells cannot communicate fully has potentially important implications for our understanding of how gene activity on chromosomes changes both during normal development and in cancerous cells. The work is published in Genes and Development.

The way that the molecules that package a cell's chromosomes are organized in order to control gene activity is known as the cell's "epigenetic state." The epigenetic state is fundamental to understanding Spradling and Lee's findings. To developmental biologists, changes in this epigenetic state ultimately explain how the cell's properties are altered during tissue maturation.

"In short, acquired epigenetic changes in a developing cell are reminiscent of the learned changes the brain undergoes during childhood," Spradling explained. "Just as it remains difficult to map exactly what happens in a child's brain as it learns, it is still very difficult to accurately measure epigenetic changes during cellular development. Not enough cells can usually be obtained that are at precisely the same stage for scientists to map specific molecules at specific chromosomal locations."

Lee and Spradling took advantage of the unsurpassed genetic tools available in the fruit fly to overcome these obstacles and provide new insight into the epigenetics of cellular development.

Using a variety of tools and techniques, they focused on cells in the fruit fly ovary and were able identify a specific gene called lsd1 that is needed for ovarian follicle progenitor cells to mature at their normal rate. The researchers found that the amount of the protein that is encoded by this gene, Lsd1, which is present in follicle progenitors decreases as the cells approach differentiation. What's more, the onset of differentiation could be shifted by changing the levels of Lsd1 protein that are present. They deduced that differentiation ensues when Lsd1 levels fall below a critical threshold, and that this likely corresponds to when genes can be stably expressed.

"The timing of differentiation is very important for normal development," Lee said. "Differentiation onset determines how many times progenitors divide, and even small perturbations in Lsd1 levels changed the number of follicle cells that were ultimately produced, which reduced ovarian function."

Previously, it was thought that the follicle cell progenitors started to differentiate based on an external signal they received from another kind of ovarian cells known as germ cells. Lee and Spradling found that while this germ cell signal was essential, it was already being regularly sent even before the progenitors responded. Instead, it was the Lsd1-mediated change in their epigenetic state that timed when progenitor cells started to respond to the signal and begun differentiating. Once they become competent, however, differentiating follicle cells communicate extensively with their neighbors, and continued to do so throughout their lives.

As is frequently the case in basic biological research, the molecules and mechanisms studied here are found in most multicellular animals and hence the researchers conclusions are likely to apply broadly throughout the animal kingdom, including in humans.

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Baby cells learn to communicate using the lsd1 gene

'Genome editing' could correct genetic mutations for future generations

Scientists at Indiana University and colleagues at Stanford and the University of Texas have demonstrated a technique for "editing" the genome in sperm-producing adult stem cells, a result with powerful potential for basic research and for gene therapy.

The researchers completed a "proof of concept" experiment in which they created a break in the DNA strands of a mutant gene in mouse cells, then repaired the DNA through a process called homologous recombination, replacing flawed segments with correct ones.

The study involved spermatogonial stem cells, which are the foundation for the production of sperm and are the only adult stem cells that contribute genetic information to the next generation. Repairing flaws in the cells could thus prevent mutations from being passed to future generations.

"We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated," said Christina Dann, associate scientist in the Department of Chemistry at IU Bloomington and a co-author of the study. "This technique corrects the mutation, theoretically leaving no other mark on the genome."

The paper, "Genome Editing in Mouse Spermatogonial Stem/Progenitor Cells Using Engineered Nucleases," was published in the online science journal PLOS-ONE.

The lead author, Danielle Fanslow, carried out the research as an IU research associate and is now a doctoral student at Northwestern University. Additional co-authors are from the Stanford School of Medicine and the University of Texas Southwestern Medical Center.

A challenge to the research was the fact that spermatogonial stem cells, like many types of adult stem cells, are notoriously difficult to isolate, culture and work with. It took years of intensive effort by multiple laboratories before conditions were created a decade ago to maintain and propagate the cells.

For the IU research, a primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material. The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.

Stem cells that had been modified in the lab were then transplanted into the testes of sterile mice. The transplanted cells grew or colonized within the mouse testes, indicating the stem cells were viable. However, attempts to breed the mice were not successful.

"Whether the failure to produce sperm was a result of abnormalities in the transplanted cells or the recipient testes was unclear," the researchers write.

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'Genome editing' could correct genetic mutations for future generations

Cell biologists discover on-off switch for key stem cell gene

Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Cell biologists discover on-off switch for key stem cell gene

BUSINESS WIRE: The 1st Meeting of the Series Bridging Biomedical Worlds: Turning Obstacles into Opportunities for …

MITTEILUNG UEBERMITTELT VON BUSINESS WIRE. FUER DEN INHALT IST ALLEIN DAS BERICHTENDE UNTERNEHMEN VERANTWORTLICH.

PARIS --(BUSINESS WIRE)-- 13.10.2014 --

Stem cells hold great promise for treating a variety of human diseases and injuries. Basic and translational stem cell research is among the most competitive fields in the life sciences. We have co-organized the first Bridging Biomedical Worlds conference of our new series of international scientific meetings: Turning Obstacles into Opportunities for Stem Cell Therapy.

The goal of this conference is to promote progress in the translation of basic stem cell research into stem cell therapies. To do this, presentations will highlight diverse areas of on-going stem cell biology research. In addition, panelists will discuss obstacles to translation and the associated risks and ethical controversies. These panels will provide a means to accelerate communication and cooperation among researchers, bioengineers, clinicians and industry scientists, and will explore ways to implement international policies, regulations and guidelines to ensure the development of safe and effective stem cell therapies worldwide. Participants will hear about the latest basic and translational stem cell research from more than 20 distinguished speakers from China, Japan, Europe and theUnited States.

This conference held in Beijing, China, October 13-15, 2014 is co-organized by the Fondation IPSEN, AAAS/Science and AAAS/Science Translational Medicine, in association withFred Gage (Salk Institute for Biological Studies) and Qi Zhou (Institute of Zoology, Chinese Academy of Sciences).

About AAAS/Science The American Association for the Advancement of Science (AAAS) is the worlds largest general scientific society and publisher of the journal Science (www.sciencemag.org) as well as Science Translational Medicine (www.sciencetranslationalmedicine.org) and Science Signaling (www.sciencesignaling.org). AAAS was founded in 1848, and includes some 261 affiliated societies and academies of science, serving 10 million individuals.Sciencehas the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The non-profit AAAS (www.aaas.org) is open to all and fulfills its mission to advance science and serve society not only by publishing the very best scientific research but also through initiatives in science policy, international programs and science education. http://www.sciencemag.org

About AAAS/Science Translational Medicine Science Translational Medicine, launched in October 2009, is the newest journal published by AAAS/Science. The goal of Science Translational Medicineis to promote human health by providing a forum for communicating the latest biomedical research findings from basic, translational, and clinical researchers from all established and emerging disciplines relevant to medicine. Despite 50 years of advances in our fundamental understanding of human biology and the emergence of powerful new technologies, the translation of this knowledge into effective new treatments and health measures has been slow. This paradox illustrates the daunting complexity of the challenges faced by translational researchers as they apply the basic discoveries and experimental approaches of modern science to the alleviation of human suffering. A major goal ofScience Translational Medicineis to publish papers that identify and fill the scientific knowledge gaps at the junction of basic research and medical application in order to accelerate the translation of scientific knowledge into new methods for preventing, diagnosing and treating human disease. http://www.sciencetranslationalmedicine.org

About the Institute of Zoology, Chinese Academy of Sciences Institute of Zoology (IOZ), Chinese Academy of Sciences (CAS), is one of the leading research institutions in China. The institute consists of 76 professors (including 2 members of Chinese Academy of Sciences), 3 state key research laboratories and 1 zoological museum. The major research areas of IOZ include animal sciences, cell membrane biology, stem cells and reproduction. The stem cell research teams of IOZ include over 10 PIs, and they mainly focus on questions related to the establishment of pluripotent stem cell lines, neural stem cell induction and regeneration, mechanism studies of pluripotency and differentiation regulation of embryonic stem cells, animal model establishment and functional studies, etc. The major achievements in the field of stem cell research made by IOZ faculties include: obtained the first healthy animal (Xiaoxiao the mouse) using induced pluripotent stem cells (iPSCs) via tetraploid complementation method, identified molecular markers for the evaluation of pluripotency levels of stem cells and the related regulatory mechanisms, achieved cell fate conversion across different germ layers, established various types of human and mouse embryonic stem cell lines, as well as the Beijing Stem Cell Bank, etc. These achievements has once been selected as one of the TIMES Top 10 Medical Breakthroughs in 2009, and twice been selected as Top 10 Breakthroughs in Science and Technology in China. The Beijing Stem Cell Bank now functions as a resource for stem cell and regenerative medicine studies, providing various types of embryonic stem cell lines, adult stem cell lines and somatic cell lines for many research groups. IOZ also hosts modern animal model research centers for pigs and monkeys, which have generated a few valuable animal models for disease mechanism studies and pharmaceutical researches. http://www.english.ioz.cas.cn

About the Fondation Ipsen Established in 1983 under the aegis of the Fondation de France, the mission of the Fondation Ipsen is to contribute to the development and dissemination of scientific knowledge. The long-standing action of the Fondation Ipsen aims at fostering the interaction between researchers and clinical practitioners, which is essential due to the extreme specialization of these professions. The ambition of the Fondation Ipsen is to initiate a reflection about the major scientific issues of the forthcoming years. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Mdecine et Recherche, dedicated to five main themes: Alzheimer's disease, neurosciences, longevity, endocrinology and cancer science. Moreover the Fondation Ipsen has started since 2007 several meetings in partnership with the Salk Institute, the Karolinska Institutet, the Massachusetts General Hospital, the Days of Molecular Medicine Global Foundation as well as with the science journals Nature, Cell and Science. The Fondation Ipsen has published over one hundred books and has awarded more than 250 prizes and research grants. http://www.fondation-ipsen.org

Fondation Ipsen For further information, please contact: Isabelle de Segonzac, Image Sept E-mail : isegonzac@image7.fr Tel. : +33 (0)1 53 70 74 70

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BUSINESS WIRE: The 1st Meeting of the Series Bridging Biomedical Worlds: Turning Obstacles into Opportunities for ...

The Stem Cell Theory of Cancer – Overview – Ludwig Center …

Research has shown that cancer cells are not all the same. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term.

The idea that cancer is primarily driven by a smaller population of stem cells has important implications. For instance, many new anti-cancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalksbut no matter how low the weeks are cut, if the roots arent taken out, the weeds will just grow back.

Another important implication is that it is the cancer stem cells that give rise to metastases (when cancer travels from one part of the body to another) and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation or chemotherapy has eliminated all observable signs of a cancer.

One component of the cancer stem cell theory concerns how cancers arise. In order for a cell to become cancerous, it must undergo a significant number of essential changes in the DNA sequences that regulate the cell. Conventional cancer theory is that any cell in the body can undergo these changes and become a cancerous outlaw. But researchers at the Ludwig Center observe that our normal stem cells are the only cells that reproduce themselves and are therefore around long enough to accumulate all the necessary changes to produce cancer. The theory, therefore, is that cancer stem cells arise out of normal stem cells or the precursor cells that normal stem cells produce.

Thus, another important implication of the cancer stem cell theory is that cancer stem cells are closely related to normal stem cells and will share many of the behaviors and features of those normal stem cells. The other cancer cells produced by cancer stem cells should follow many of the rules observed by daughter cells in normal tissues. Some researchers say that cancerous cells are like a caricature of normal cells: they display many of the same features as normal tissues, but in a distorted way. If this is true, then we can use what we know about normal stem cells to identify and attack cancer stem cells and the malignant cells they produce. One recent success illustrating this approach is research on anti-CD47 therapy.

Next Section >> Case Study: Leukemia

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The Stem Cell Theory of Cancer - Overview - Ludwig Center ...

ABRING Announces Debut of Stem Cell Based Skin Care Products

Manhattan NY (PRWEB) December 13, 2014

ABRING, one of the pioneers in the new era of the most advanced skin care trend, announced the debut of their two new skin care products: ABRING lemon stem cell acne serum and ABRING apple stem cell serum/eyes serum, These two new cutting-edge skin care products contain concentrated essence which is derived from Californias organic plants and has no artificial or chemical components. This condensed essence has been widely recognized for its obvious effect on anti-aging and stimulation of skin cells regeneration. As a result, ABRINGs new stem cell products not only have such distinctive functions as anti-aging, supplementing moisture, alleviating scars appearance and whitening skin, but also can be safely used by pregnant women since it only contains pure natural plant ingredients.

It is well-known that the skin is exposed to all kinds of radiations everyday which can damage our skin in various ways. Most people think that there is nothing to worry because they have already used segregation frost. However, what they dont realize is the fact that segregation frost only plays a trivial role in isolation and doesnt help repair or stimulate skin cells renewal or regeneration activities.

Stem cells are capable of self-reproducing and have lots of potentials. Under different conditions, they can evolve into various functional cells. Therefore, the activity of skin stem cells directly affects the external appearance of the skin. ABRING uses the newest stem cell research achievement and is a known brand for natural beauty products. Because it contains condensed essences concentrated from organic plants and is free of any chemicals, ABRING can stimulate activity in skin cells, slow down the aging process, increase elasticity, improve tone, and reduce the appearance of scars. In addition, because ABRING also contains a lot of mineral water and vitamin C, it can effectively improve skin brightening and help cure and prevent acne.

ABRING products founder, Albert, born in California, United, is a cell biologist and a biochemist. Unlike many, he didnt have a carefree and happy childhood as the result of a natural disaster. However, Albert wasnt defeated by the unpredicted distress. Instead, he was dedicated to study and graduated from Columbia University. In 1971, invited by the U.S. government, Doctor Albert became one of first post-war medical doctors. In same year, Doctor Albert established ABRING laboratory which stands for: Doctor Albert brings hope. Based on years of research at Columbia University focusing on stem cell biology, Doctor Albert found that certain raw materials can effectively remove skin scars without using any chemical additives. After over 7000 experiments, he finally extracted pure activating factors from natural plants that can help alleviate the appearance of scars. Dr. Albert named the condensed essence of concentration of plant stem cells as ABRING. Since then, with its innovative and effective way of enhancing the tone of skin, ABRING started to be recognized more and more by the world. Doctor Albert's efforts eventually got paid off and ABRING became one of the favored skin care products from the users of all classes. Nowadays, ABRING has been used by more than 500 famous beauty salons over the world. Moreover, the product has been widely recommended by doctors as daily lotion for skin disease treatment or post-surgery care.

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ABRING Announces Debut of Stem Cell Based Skin Care Products

Royan using stem cells to treat kidney diseases

Source: Islamic Republic News Agency

Iranian researchers at Royan Institute are conducting clinical trials to treat chronic and acute kidney disease by using mesenchymal stem cells, an official said.

Royan Institute

Speaking on the sidelines of the 12th Asian Congress of Urology (ACU), Dr. Reza Moqaddas-Ali, the head of Kidney Group of Stem Cells Research Center affiliated to Royan Institute, added that the researchers have conducted animal trials successfully.

"Results of animal trials showed that mesenchymal stem cell treatment has been found to be a good treatment for acute kidney injury," he said.

"The treatment was not very effective in treating chronic kidney disease, but helps prevent progression of acute kidney injury to advanced chronic kidney disease."

Chronic kidney disease, also known as chronic renal disease, is a progressive loss in renal function over a period of months or years.

Acute kidney injury (AKI) is an abrupt loss of kidney function that develops within seven days.

Kidney Diseases

The ACU took place on Kish Island in southern Iran from December 5 to 9.

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Royan using stem cells to treat kidney diseases

Scientists make stem cell breakthrough

Sydney, Dec 11 (IANS): An Australian research team together with international scientists has discovered a new stem cell that can be programmed to become any part of the body.

The ramifications of the find mean that a transplant can be conducted by using the patient's own cells, which can be made into organs and tissue.

The discovery, published in the journal Nature Thursday, is a breakthrough in stem cell research.

"These are remarkably useful cells, because you can apply them to several different areas of medicine," Xinhua quoted molecular biologist Thomas Preiss, from the Australian National University, as telling Fairfax Media.

More than 50 researchers from Australia, Canada, the Netherlands and South Korea worked in the study, known as Project Grandiose, which identified the pluripotent stem cell.

The new cell is considered a potential prototype for the mass production of therapeutic stem cells to treat a huge range of illnesses and injuries.

Medical conditions such as blindness, Parkinson's, Alzheimer's, stroke and spinal cord injury will be major beneficiaries of the new find.

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Scientists make stem cell breakthrough

Unlocking the secrets of stem cell generation

14 hours ago Professor Thomas Preiss discusses gene networks during stem cell reprogramming with his JCSMR colleagues Dr Jen Clancy and Dr Hardip Patel. Credit: Stuart Hay.

International scientists have carried out the most detailed study of how specialised body cells can be reprogrammed to be like cells from the early embryo.

The findings are a major advance in stem cell science and could help usher in a new era of regenerative medicine, where a small sample of a patient's cells could be used to grow new tissues and organs for transplant.

"This kind of work will speed up the development of treatments for many illnesses that currently have no cure," said Professor Thomas Preiss from The John Curtin School of Medical Research.

"It could one day lead to treatments for age-related macular degeneration, Parkinson's, Alzheimer's, spinal cord injury, stroke, diabetes, blood and kidney diseases, and many others which are associated with tissue damage and cell loss."

Professor Preiss and the team at ANU were part of the international consortium known as Project Grandiose, which mapped the detailed molecular process involved in the generation of induced pluripotent stem cells (iPS).

The discovery that body cells can in principle be coaxed to become iPS cells led to the award of the Nobel Prize for Physiology or Medicine in 2012. Since then there has been a surge in global research to better understand iPS cell reprogramming, as it might help avoid the ethically-sensitive use of embryo-derived cells.

"The race is on to make reprogramming a safe and efficient process so that the resulting stem cells can be broadly applied in therapies," Professor Preiss said.

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"We have described in unprecedented detail the molecular changes that cells undergo as they reprogram into stem cells and also discovered a new kind of pluripotent cell that can be seen as a prototype for therapeutic cell production."

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Unlocking the secrets of stem cell generation