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A way to stabilize haploidy in animal cells – Phys.Org

By Embryonic Stem Cells

August 15, 2017 SKY analysis of haploid and diploid cells. Credit: CNIO

The emergence in recent years of the first mammalian haploid cell lines has raised great expectations in the scientific community. Despite their potential, these cultures present some issues that complicate their use because haploidy is unstable and can be lost quickly. The Genomic Instability Group at the Spanish National Cancer Research Centre (CNIO) has offered an explanation of this phenomenon and proposes a way to overcome it. This work has been published in the journal Proceedings of the National Academy of Sciences (PNAS).

With the exception of the sperm or ovules, cells contain two sets of chromosomes, one from each parent. However, organisms with a single set of chromosomes (haploids), such as yeast, are extremely useful for genetic studies and are crucial in identifying key genes and pathways. Laboratory yeasts enabled studies on autophagy by Yoshinori Ohsumi, which earned him the Nobel Prize in Medicine in 2016, and the Nobel-winning discovery of the cell cycle regulatory genes.

"As [yeast] has only one set of chromosomes, it is very easy to find interesting mutants, as all you have to do is to alter a single allele to produce a phenotype," says Oscar Fernndez-Capetillo, head of the Genomic Instability Group and the leader of the research project. "In mammals, in the absence of haploid cells, other approaches have been used to identify key genes, such as interfering RNA, but they are sub-optimal methods. All this changed five years ago when haploid cells were discovered in a leukaemia patient (KBM7 and HAP1) and with the emergence of techniques to create mammalian haploid embryonic stem cells, developed originally by Anton Wutz," continues Fernndez-Capetillo.

However, the cultures of such mammalian haploid cells become diploid within a few days. This phenomenon, which has been called "diploidization," is what Fernndez-Capetillo's group has been studying. Their findings suggest that the loss of haploid cells is due to their limited viability, and therefore, they are replaced by existing diploid cells in the cultures.

"When you try to isolate haploid cells, it is very difficult to take only one; you usually separate several so you always drag along a diploid. When you culture them, you invariably observe that the haploid cells die and the diploid cells become the majority," he says. "We now know that this happens because the haploid cells activate death mechanisms via p53."

Their studies show that the problem arises when the haploid cells try to separate their chromosomes during mitosis. The machinery involved in cell division has been designed to handle a fixed amount of DNA (46 chromosomes). When there is more (polyploidy) or less (haploidy), mitosis is more prone to errors during the segregation of the chromosomes, and this activates p53. This is the reason why haploid cell cultures do not thrive. By eliminating p53, as this study demonstrates, haploid cells are able to survive.

"Our findings should facilitate the use of animal haploid cells, making them accessible to a broader range of laboratories and technologies," the authors conclude. Currently, the group is trying to discover chemical forms of stabilizing haploidy in animal cells and is exploring strategies that would allow the creation of organs or even animals that only have a maternal set of chromosomes.

Explore further: First 'haploid' human stem cells could change the face of medical research

More information: A p53-dependent response limits the viability of mammalian haploid cells Proceedings of the National Academy of Sciences (2017). http://www.pnas.org/cgi/doi/10.1073/pnas.1705133114

Journal reference: Proceedings of the National Academy of Sciences

Provided by: Centro Nacional de Investigaciones Oncolgicas

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The emergence in recent years of the first mammalian haploid cell lines has raised great expectations in the scientific community. Despite their potential, these cultures present some issues that complicate their use because ...

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A way to stabilize haploidy in animal cells - Phys.Org

Adult brains produce new cells in previously undiscovered area – Medical Xpress

By Adult Stem Cells

August 15, 2017 Credit: Wikimedia Commons

A University of Queensland discovery may lead to new treatments for anxiety, depression and post-traumatic stress disorder (PTSD). UQ Queensland Brain Institute scientists have discovered that new brain cells are produced in the adult amygdala, a region of the brain important for processing emotional memories.

Disrupted connections in the amygdala, an ancient part of the brain, are linked to anxiety disorders such as PTSD.

Queensland Brain Institute director Professor Pankaj Sah said the research marked a major shift in understanding the brain's ability to adapt and regenerate.

"While it was previously known that new neurons are produced in the adult brain, excitingly this is the first time that new cells have been discovered in the amygdala," Professor Sah said.

"Our discovery has enormous implications for understanding the amygdala's role in regulating fear and fearful memories."

Researcher Dr Dhanisha Jhaveri said the amygdala played a key role in fear learningthe process by which we associate a stimulus with a frightening event.

"Fear learning leads to the classic flight or fight responseincreased heart rate, dry mouth, sweaty palmsbut the amygdala also plays a role in producing feelings of dread and despair, in the case of phobias or PTSD, for example," Dr Jhaveri said.

"Finding ways of stimulating the production of new brain cells in the amygdala could give us new avenues for treating disorders of fear processing, which include anxiety, PTSD and depression."

Previously new brain cells in adults were only known to be produced in the hippocampus, a brain region important for spatial learning and memory.

The discovery of that process, called neurogenesis, was made by Queensland Brain Institute founding director Professor Perry Bartlett, who was also involved in the latest research.

"Professor Bartlett's discovery overturned the belief at the time that the adult brain was fixed and unable to change," Professor Sah said. "We have now found stem cells in the amygdala in adult mice, which suggests that neurogenesis occurs in both the hippocampus and the amygdala. "The discovery deepens our understanding of brain plasticity and provides the framework for understanding the functional contribution of new neurons in the amygdala," Professor Sah said.

The research, led by Professor Sah, Professor Bartlett and Dr Jhaveri, is published in Molecular Psychiatry.

Explore further: PTSD may be physical and not only psychological

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Adult brains produce new cells in previously undiscovered area - Medical Xpress

Adult brain’s fear HQ can grow new cells – Cosmos

By Adult Stem Cells

A new cradle of brain cell formation has been discovered in the adult amygdala, a region that gives memories their emotional bite.

The discovery could lead to a deeper understanding of post-traumatic stress disorder, anxiety, and phobias and also to better treatments.

The formation of freshly minted neurons the cells that send and receive signals in the brain was long thought to be non-existent in adults. But that dogma was overturned in the early 1990s with the discovery of neuron-forming stem cells in the adult hippocampus, a seahorse-shaped region that acts as the brains memory hub. The smell-processing olfactory bulb in rodents, at least also churns out baby neurons throughout life.

Now, the almond-shaped amygdala can be added to this select club.

Our discovery has enormous implications for understanding the amygdala's role in regulating fear and fearful memories," says Pankaj Sah of the Queensland Brain Institute at the University of Queensland, one of the studys lead authors.

The amygdala plays an important role in imbuing memories with emotion. This helps us to learn from our experiences, but the process can go awry in post-traumatic stress disorder, anxiety, or phobias. In these conditions, fear can overwhelm, thanks to an overzealous amygdala.

Researchers have had inklings that the amygdala can make new neurons. But the new work, published in Molecular Psychiatry, is the first to clearly show that stem cells forming in the mouse amygdala grow into bona fide, fully functioning neurons, which is actually pretty revolutionary, says Jee Kim from the Florey Institute of Neuroscience & Mental Health at the University of Melbourne, who was not involved in the study.

The discovery is likely to hold true for the similarly wired human amygdala, says Dhanisha Jhaveri of the Queensland Brain Institute, who co-led the study.

The amygdala only contains a small number of these newborn cells fewer than in the hippocampus. But even small numbers could have a big impact," says Jhaveri.

Thats because the newly formed cells are interneurons, cells that dampen down activity in neural circuits. In the amygdala, these cells help to keep emotions like fear in check.

Now that the fledgling neurons have been discovered, the researchers are working to nut out the pulleys and levers that control their formation. In the hippocampus, exercise and antidepressant drugs can spur new cell formation, whereas stress and inflammation stymy the process.

Similar triggers could affect neurogenesis in the amygdala, too, says Jhaveri. Understanding these triggers, and identifying drugs that specifically encourage new cell formation in the amygdala could ultimately lead to better treatments for anxiety-related disorders.

The finding could also help to explain why exposure therapy, designed to gradually dampen a persons response to a phobia or traumatic memory, works, according to Kim. These neurons may be important in how we learn to reduce our fear, she says.

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Adult brain's fear HQ can grow new cells - Cosmos

Cardiac stem cells rejuvenate rats’ aging hearts, study says – CNN – CNN

By Uncategorized

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Cardiac stem cells rejuvenate rats' aging hearts, study says - CNN - CNN

CAR T-Cell Therapy Shown to Eliminate Tumors in Some Chronic Lymphocytic Leukemia Patients During Trial – Lymphoma News Today

By Uncategorized

CAR T-cell immunotherapy was seen to eradicate or shrink tumors in 70% of patients with chronic lymphocytic leukemia (CLL) who had exhausted other treatment options, according to a clinical trial report.

Among those who had no sign of cancer left in the bone marrow four weeks after treatment, all had survived with no signs of cancer after six months.

Researchers at the Fred Hutchinson Cancer Research Center also suggested, based on the studies, that analyzing bone marrow using a new genetic technique is a better method than the more commonly used cell counts when attempting to determine a prognosis for the disease.

The report,Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen ReceptorModified T Cells After Failure of Ibrutinib,described the outcomes of 24 CLL patients whose cancer had progressed after treatment with Imbruvica (ibrutinib), which was approved for the treatment of CLL in 2014. The research was published in theJournal of Clinical Oncology.

It was not known whether CAR T-cells could be used to treat these high-risk CLL patients, Cameron Turtle, an immunotherapy researcher at Fred Hutch and lead author of the study, said in apress release. Our study shows that CD19 CAR T-cells are a highly promising treatment for CLL patients who have failed ibrutinib.

CD19 is a molecule found on the surface of leukemia cells. T-cells, gathered from a patient, are engineered to specifically recognize this factor. When that happens, the body launches an aggressive immune response toward these cancer cells.

The Phase 1/2 study (NCT01865617) which is still recruiting participants included patients who had failed a median of five previous treatment rounds. The participants ages ranged from 40 to 73.

Before injecting the engineered T-cells into patients, their white blood cells were destroyed by chemotherapy.

One patient had a severe toxic response to the treatment and was not assessed for the therapys effects. Among the remaining patients, 16 of 23 70% had a response four weeks after treatment.

Not all patients had chemotherapy before CAR T-cell treatment, but among the 19 who did, four had a complete response, and 10 had a partial response.

Two additional patients responded after a second round of chemotherapy and CAR T-cell treatment.

Analyzing bone marrow using a method that can sort cancerous cells from normal cells indicated that 88% were free of disease after treatment. But repeating the analysis in 12 of these patients using a method called IGH deep sequencing showed that only 58% of them had no disease present in the bone marrow.

Those in which the genetic analysis found no traces of cancer all survived with no further traces of disease for a median of 6.6 months after treatment.

For more information about the trial, which also includes patients with relapsed or refractory non-Hodgkins lymphoma or acute lymphoblastic leukemia, see the trial registration page at thislink. The trial treats patients at theSeattle Cancer Care Allianceclinic.

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CAR T-Cell Therapy Shown to Eliminate Tumors in Some Chronic Lymphocytic Leukemia Patients During Trial - Lymphoma News Today

Stem cell therapy may help knees – News – Citizens’ Voice – Citizens Voice

By Uncategorized

Q: I read that you can use your own stem cells to rejuvenate worn-out knees. Does this really work?

A: Worn out is a good way to term what happens to the knee joint with prolonged use. Lets look at how this happens, starting with cartilage.

The lower portion of the knee joint (at the tibia) contains shock absorbers called menisci made of cartilage. You have one on the inner portion and another on the outer portion of each knee. The upper portion of the knee joint (at the femur) is lined with cartilage as well. All of this cartilage helps protect the bones at the joint but it doesnt heal or regenerate well due to limited blood supply. When severe, worn cartilage leads to arthritis of the knee. In knee X-rays of people over age 60, 37 percent have shown evidence of arthritis of the knees.

The intriguing thing about stem cells is that they have the ability to become any type of cell that the body needs. The cells used for stem cell injections in the knees are called mesenchymal stem cells, and they can differentiate into bone, fat or cartilage cells. These stem cells can come from the fat cells of your body, from your bone marrow or from the inner lining of your knee joint; theyre then replicated in the laboratory and injected into the knee joint.

Heres what the research shows so far.

In a 2013 study, 32 patients with meniscal tears of the knee were injected with a combination of stem cells, platelet-rich plasma and hyaluronic acid. The study reported improved symptoms and even MRI evidence of meniscal cartilage regeneration.

In a 2014 study, 55 patients who had surgery for meniscal tears of the knees were separated into three groups, with two of the groups receiving stem cell injections. Researchers found that, after six weeks, pain had decreased substantially in the two groups that received stem cell injections and that the decrease was even greater at one and two years after the injection.

In a 2017 study in the British Journal of Sports Medicine, researchers analyzed six studies that used stem cells for osteoarthritis of the knees. In five of the studies, stem cells were given after surgery to the knee; in the other study, stem cells from a donor were administered without surgery. All the studies showed reduced pain and improved knee function. Further, in three of the four trials, MRIs corroborated the cartilage improvements.

There may be benefit to stem cell injections for cartilage loss of the knees, but more data are needed. Id also like to see more data on this type of therapy as a preventive measure for younger patients before their knees are worn out.

ASK THE DOCTORS is written by Robert Ashley, M.D., Eve Glazier, M.D., and Elizabeth Ko, M.D. Send questions to askthedoctors@

mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095.

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Stem cell therapy may help knees - News - Citizens' Voice - Citizens Voice

2m collaboration to focus on gene and cell therapy – Drug Target Review

By Uncategorized

news

A leading gene and cell therapy group has announced a collaboration focusing on gene and cell therapy manufacturing..

A leading gene and cell therapy group, has announced it has agreed to enter into a collaboration agreement with a consortium of partners, the agreement is a two-year 2 million collaboration project focused on gene and cell therapy manufacturing, co-funded by the UKs innovation agency, Innovate UK.

Cell and gene therapies offer unprecedented promise for the cure, treatment or long-term management of disease and we are delighted that this consortium has been awarded funding from Innovate UK that will help to keep Oxford BioMedica (OXB), our partners and the UK, at the forefront of innovation in industrial viral vector manufacturing., said John Dawson, Chief Executive Officer of Oxford BioMedica.

The aim of the collaboration is to explore and apply novel advanced technologies to further evolve OXBs proprietary suspension LentiVector platform to deliver even higher quality vectors for both clinical and commercial use. The project aims to deliver tangible benefits to patients by shortening the time-to-clinic and time-to-market as well as to improve the cost and access of bringing novel gene and cell therapies to patients.

Each partner in the collaboration holds proprietary technology and know-how that can be used to develop an innovative approach to viral vector manufacturing.

Collaborating on developing improved process analytic technologies with our partners will help drive productivity in viral vector manufacturing, accelerating the development of these transformative advanced therapies. We have the opportunity to both transform patients lives and grow an industry in the UK that we can be proud of,said Keith Thompson, Chief Executive Officer of Cell and Gene Therapy Catapult.

The aims of this pioneering project are closely aligned with the current government national priorities to make the UK a global hub for manufacturing advanced therapies, which will benefit economic growth and create and retain more highly skilled employment.

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2m collaboration to focus on gene and cell therapy - Drug Target Review

How Do We Get Pluripotent Stem Cells? | Boston Children’s …

By Induced Pluripotent Stem Cells

Pluripotent stem cells can be created in several ways, depending on the type.

Genetic reprogramming (induced pluripotent cells): Several labs, including that of George Q. Daley, MD, PhD, Director of Stem Cell Transplantation Program, have shown that it requires only a handful of genes to reprogram an ordinary cell from the body, such as a skin cell, into whats known as an induced pluripotent cell (iPS cell). Currently, these genes (Oct4, Sox2, Myc, and Klf4) are most commonly brought into the cell using viruses, but there are newer methods that do not use viruses.

Although skin cells are probably the number-one source of iPS cells currently, lines are also being created from blood cells and mesenchymal stem cells (a type of multipotent adult stem cell that gives rise to a variety of connective tissues). Laboratories in the Stem Cell Program at Childrens Hospital Boston are exploring whether iPS lines made from different kinds of patient cells are easier to work with, or can more readily form the particular kind of cell a patient might need for treatment.

Childrens researchers are also continuing to experiment with more efficient programming techniques, so they can get a higher yield of true pluripotent stem cells.

IVF donations of unused/discarded embryos (ES cells): Another major source of pluripotent stem cells for research purposes is unused embryo donated by couples undergoing in vitro fertilization (IVF). Some of these may be poor-quality embryos that would otherwise be discarded. The resulting cells are considered to be true embryonic stem cells (ES cells).

The donated embryos are placed in a media preparation in special dishes and allowed to develop for a few days. At about the fifth day the embryo reaches the blastocyst stage and forms a ball of 100-200 cells. At this stage, ES cells are derived from the blastocysts inner cell mass. In some cases, the ES cells can be isolated even before the blastocyst stage.

To date, Childrens has created more than a dozen new ES cell lines using this approach, which we are now making available to other scientists. These ES cells are not genetically matched to a particular patient, but instead are used to advance our knowledge of how stem cells behave and differentiate.

Some people question the ethics of using discarded IVF embryos for research. For more discussion, see Policy and Ethics.

Somatic cell nuclear transfer: The process called nuclear transfer involves combining a donated human egg with a cell from the body (typically a skin cell) to create a type of embryonic stem cell, sometimes called an ntES cell. Nuclear transfer requires an egg donor.

First, an incredibly thin microscopic needle is used to remove the eggs nucleus, which contains all the eggs genetic material, and replace it with the nucleus from the body cell. The process of transferring the nucleus into the egg reprograms it, reactivating the full set of genes for making all the tissues of the body. How this happens isnt well understood yet, and researchers in the Stem Cell Program at Boston Childrens Hospital are trying to understand it better.

Next, the resulting reprogrammed cell is encouraged to develop and divide in the lab, and by about day five, it forms a blastocyst, a ball of 100-200 cells. The inner cells of the blastocyst are then isolated to create ntES cells.

Of all the techniques for making pluripotent cells, nuclear transfer is the most technically demanding and therefore the least efficient. To date, it has only been successful in lower animals, not in humans. But because the stem cells created would be an exact genetic match to the patient, nuclear transfer may eliminate the tissue matching and tissue rejection problems that are currently a serious obstacle to successful tissue transplantation. For this reason, nuclear transfer is an important area of research at Childrens.

Because ntES cells created from human patients would match them genetically, nuclear transfer is sometimes called therapeutic cloningnot to be confused with the concept of reproductive cloning.

Parthenogenesis (unfertilized eggs): Using a series of chemical treatments, its possible to trick an egg into developing into an embryo without being fertilized by sperm. This process, called parthenogenesis, sometimes happens in nature, allowing many plants and some animals to reproduce without the contribution of a male.

By inducing parthenogenesis artificially, researchers have been able to create parthenogenetic embryonic stem cells, or pES cells, in mice. The embryos created, known as parthenotes, are grown for about five days until they reach the blastocyst stage. Development is then stopped and pES cells were derived from the blastocysts inner core of cells.

Parthenogenesis hasnt been accomplished in human eggs yet, at least not by choice (a Korean team is thought to have created human pES cells accidentally in 2007). But researchers at Childrens are trying to do so, since pES cells, if carefully typed genetically, could potentially be used to create master banks of pluripotent stem cells. Doctors could then choose a cell line thats genetically compatible with the patients immune system. (For details, see How do pluripotent stem cells get turned into treatments?).

Of more immediate concern is the possibility that parthenogenesis could be used to make pES cells for the egg donor herself or a sibling. However, before using these cells in patients, researchers need to know more about the safety of this approach.

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MESO-BRAIN initiative receives 3.3million to replicate brain’s neural networks through 3D nanoprinting – Cordis News

By Induced Pluripotent Stem Cells

The MESO-BRAIN consortium has received a prestigious award of 3.3million in funding from the European Commission as part of its Future and Emerging Technology (FET) scheme. The project aims to develop three-dimensional (3D) human neural networks with specific biological architecture, and the inherent ability to interrogate the networks brain-like activity both electrophysiologically and optically.

The MESO-BRAIN projects cornerstone will use human induced pluripotent stem cells (iPSCs) that have been differentiated into neurons upon a defined and reproducible 3D scaffold to support the development of human neural networks that emulate brain activity. The structure will be based on a brain cortical module and will be unique in that it will be designed and produced using nanoscale 3D-laser-printed structures incorporating nano-electrodes to enable downstream electrophysiological analysis of neural network function. Optical analysis will be conducted using cutting-edge light sheet-based, fast volumetric imaging technology to enable cellular resolution throughout the 3D network. The MESO-BRAIN project will allow for a comprehensive and detailed investigation of neural network development in health and disease.

The MESO-BRAIN project will launch in September 2016 and research will be conducted over three years.

The MESO-BRAIN initiative targets a transformative progress in photonics, neuroscience and medicine. The project aims to develop human induced pluripotent stem cell (iPSC)-derived neural networks upon a defined and reproducible 3D scaffold to emulate brain activity and improve our understanding and treatment of conditions such as Parkinsons disease, dementia and trauma. This research, led by Aston University, is a collaboration between Axol Bioscience Ltd. (UK), Laser Zentrum Hannover (Germany), University of Barcelona (Spain), Institute of Photonic Sciences (Spain) and KITE Innovation (UK). The project is funded by the European Commission through its Future and Emerging Technology (Open) programme.

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MESO-BRAIN initiative receives 3.3million to replicate brain's neural networks through 3D nanoprinting - Cordis News

induced pluripotent stem cell (iPS cell) | biology …

By Induced Pluripotent Stem Cells

Alternative Title: iPS cell

Induced pluripotent stem cell (iPS cell), immature cell that is generated from an adult (mature) cell and that has regained the capacity to differentiate into any type of cell in the body. Induced pluripotent stem cells (iPS cells) differ from embryonic stem cells (ES cells), which form the inner cell mass of an embryo but also are pluripotent, eventually giving rise to all the cell types that make up the body. Induced pluripotent cells were first described in 2006 by Japanese physician and researcher Shinya Yamanaka and colleagues. The first experiments were performed by using mouse cells. The following year, however, Yamanaka successfully derived iPS cells from human adult fibroblast cells. Until that time, human stem cells could be obtained only by isolating them from early human embryos. Hence, an important feature of iPS cells is that their generation does not require an embryo, the use of which is fraught with ethical issues.

The generation of iPS cells from somatic cells (fully differentiated adult cells, excluding germ cells) was based on the idea that any cell in the body can be reprogrammed to a more primitive (stemlike) state. Among the first to discover that possibility was British developmental biologist John B. Gurdon, who in the late 1950s had shown in frogs that egg cells are able to reprogram differentiated cell nuclei. Gurdon used a technique known as somatic cell nuclear transfer (SCNT), in which the nucleus of a somatic cell is transferred into the cytoplasm of an enucleated egg (an egg that has had its nucleus removed). In 1996 British developmental biologist Ian Wilmut and colleagues used SCNT to create Dolly the sheep, the first clone of an adult mammal. The experiments with SCNT were crucial to the eventual production of iPS cells. Indeed, by the time of Dollys creation, it was widely accepted that factors in the egg cytoplasm were responsible for reprogramming differentiated cell nuclei. The factors controlling the process were unknown, however, until Yamanaka published his first report describing iPS cell generation. (Yamanaka and Gurdon shared the 2012 Nobel Prize for Physiology or Medicine for their discoveries.)

Several proteins have been identified that are capable of inducing or enhancing pluripotency in nonpluripotent (i.e., adult) cells. Of key importance are the transcription factors Oct-4 (octamer 4) and Sox-2 (sex-determining region Y box 2), which maintain stem cells in a primitive state. Other proteins that may be used to enhance pluripotency include Klf-4 (Kruppel-like factor 4), Nanog, and Glis1 (Glis family zinc finger 1).

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stem cell: Induced pluripotent stem cells

Due to the ethical and moral issues surrounding the use of embryonic stem cells, scientists have searched for ways to reprogram adult somatic cells. Studies of cell fusion, in which differentiated adult somatic cells grown in culture with embryonic stem cells fuse with the stem cells and acquire embryonic stem-cell-like properties, led to the idea that specific genes could reprogram...

Pluripotency factors can be introduced into nonpluripotent cells in different ways, such as by plasmids or delivery as proteins or modified RNAs. Among the most effective and widely used methods, however, is delivery via a retroviral vector. Retroviral vectors can readily enter cells, making the genes they carry accessible to the cell; other retroviral activities are silenced. However, because retroviruses integrate into the nuclear genome, their use raises the risk of virus-induced tumour formation. Nonetheless, retroviral delivery remains highly effective, and technical advances to prevent the integration of retroviral material into the nuclear genome have allowed for the generation of iPS cells via ectopic expression (in the cytoplasm) of retrovirus-delivered transcription factors. Ectopic expression also has been achieved with the use of recombinant adeno-associated virus.

Since the initial development of iPS cells, researchers have been working to improve the techniques and to learn what drives pluripotent stem cells to differentiate in particular ways. They also have been investigating the use of iPS cells in the treatment of certain diseases. Of significance is the potential to create patient-specific iPS cells (using a patients own adult cells), which could allow for the generation of perfectly matched cells and tissues for transplantation therapies. Such therapies could help overcome the risk of immune rejection, which is a major challenge in regenerative medicine.

an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There...

...in animals. This is primarily because of the technical challenges and ethical controversy arising from the procuring of human eggs solely for research purposes. In addition, the development of induced pluripotent stem cells, which are derived from somatic cells that have been reprogrammed to an embryonic state through the introduction of specific genetic factors into the cell nuclei, has...

...into pluripotent stem cells. Examples of these factors include Oct-4 (octamer 4), Sox-2 (sex-determining region Y box 2), Klf-4 (Kruppel-like factor 4), and Nanog. Reprogrammed adult cells, known as induced pluripotent stem (iPS) cells, are potential autogeneic sources for cell transplantation and bioartificial tissue construction. Such cells have since been created from the skin cells of...

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induced pluripotent stem cell (iPS cell) | biology ...

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