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Scientists from the German Cancer Research Center (DKFZ) and the stem cell institute HI-STEM* in Heidelberg have succeeded for the first time in directly reprogramming human blood cells into a previously unknown type of neural stem cell. These induced stem cells are similar to those that occur during the early embryonic development of the central nervous system. They can be modified and multiplied indefinitely in the culture dish and can represent an important basis for the development of regenerative therapies.

Stem cells are considered to be the all-rounders of our tissues: they can multiply indefinitely and then -- if they are pluripotent embryonic stem cells -- generate all conceivable cell types. In 2006, the Japanese scientist Shinya Yamanaka recognized that such cells could also be produced in the laboratory -- from mature body cells. Four genetic factors alone are sufficient to reverse the course of development and produce so-called induced pluripotent stem cells (iPS) that have identical properties to embryonic stem cells. Yamanaka was awarded the Nobel Prize for Medicine in 2012 for this discovery.

"This was a major breakthrough for stem cell research," said Andreas Trumpp, German Cancer Research Center (DKFZ) and Director of HI-STEM in Heidelberg. "This applies in particular to for research in Germany, where the generation of human embryonic stem cells is not permitted. Stem cells have enormous potential both for basic research and for the development of regenerative therapies that aim to restore diseased tissue in patients. However, reprogramming is also associated with problems: For example, pluripotent cells can form germ line tumors, so-called teratomas.

Another possibility is not to completely turn back the course of development. For the first time, Trumpp's team has succeeded in reprogramming mature human cells in such a way that a defined type of induced neural stem cells is produced that can multiply almost indefinitely. "We used four genetic factors like Yamanaka, but different ones for our reprogramming," explains Marc Christian Thier, first author of the study. "We assumed that our factors would allow reprogramming to an early stage of development of the nervous system."

In the past, other research groups also reprogrammed connective tissue cells into mature nerve cells or neural precursor cells. However, these artificially produced nerve cells often could not be expanded and could therefore hardly be used for therapeutic purposes. "Often, it was a heterogeneous mixture of different cell types that might not exist in the body under physiological conditions," said Andreas Trumpp explaining the problems.

Together with stem cell researcher Frank Edenhofer from the University of Innsbruck and neuroscientist Hannah Monyer from DKFZ and the Heidelberg University Hospital, Trumpp and his team have succeeded in reprogramming different human cells: connective tissue cells of the skin or pancreas as well as peripheral blood cells. "The origin of the cells had no influence on the properties of the stem cells," said Thier. In particular, the possibility of extracting neural stem cells from the blood of patients without invasive intervention is a decisive advantage for future therapeutic approaches.

What is special about the reprogrammed cells of the Heidelberg researchers is that they are a homogeneous cell type that resembles a stage of neural stem cells that occurs during the embryonic development of the nervous system. "Corresponding cells exist in mice and probably also in humans during early embryonic brain development," said Thier. "We have described here a new neural stem cell type in the mammalian embryo.

These so called "induced Neural Plate Border Stem Cells" (iNBSCs) have a broad development potential. The iNBSCs of the Heidelberg scientists are expandable and multipotent and can develop in two different directions. On the one hand, they can take the path of development to mature nerve cells and their supplier cells, the glial cells, i.e. become cells of the central nervous system. On the other hand, they can also develop into cells of the neural crest, from which different cell types emerge, for example peripheral sensitive nerve cells or cartilage and bones of the skull.

The iNBSCs thus form an ideal basis for generating a broad range of different cell types for an individual patient. "These cells have the same genetic material as the donor and are therefore presumably recognized as "self" by the immune system and are not rejected," explains Thier.

The CRISPR/Cas9 gene scissors can be used to modify the iNBSC or repair genetic defects, as the scientists have shown in their experiments. "They are therefore of interesting both for basic research and the search for new active substances and for the development of regenerative therapies, for example in patients with diseases of the nervous system. However until we can use them in patients, a lot of research work will still be necessary," emphasizes Trumpp.

Date: December 21, 2018
Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
Summary: Scientists have succeeded for the first time in directly reprogramming human blood cells into a previously unknown type of neural stem cell. These induced stem cells are similar to those that occur during the early embryonic development of the central nervous system. They can be modified and multiplied indefinitely in the culture dish and can represent an important basis for the development of regenerative therapies.

The steady production of sperm relies on the number of sperm stem cells in the testis remaining constant. Researchers including Asst. Prof. Yu Kitadate and Prof. Shosei Yoshida (developmental biologists at the National Institute for Basic Biology within the National Institutes of Natural Sciences in Japan) and Prof. Benjamin Simons (a theoretical physicist at the University of Cambridge in the UK) have revealed a novel mechanism for stem cell number control. Their results show that constant sperm stem cell numbers are achieved, in mouse testes, through a self-organized process in which they actively migrate and compete for a limited supply of self-renewal-promoting fibroblast growth factors (FGFs). This study was published on line in Cell Stem Cell on Nov. 20th, 2018.

To ensure a balance between the loss of differentiated cells and their replacement in long-lived multicellular organisms, it is critically important to keep the number of tissue stem cells constant. Failure to maintain stem cell number is thought to underlay the progression of ageing and disease. In tissues like the testis and ovary of the fruitfly Drosophila and intestine of mammalians, stem cells are clustered in their specialized home where self-renewal-promoting factors are abundant: the stem cell niche. In these tissues, stem cell numbers are controlled simply by the capacity of the niche. However, sperm stem cells are not clustered in mouse testis, but are highly motile and widely dispersed across the basement membrane. Yet, their density remains surprisingly uniform thus raising the question of how their numbers are regulated.

In this study, the researchers found that a subset of lymphatic endothelial (LE) cells produce FGFs (Fgf5, 8 and 4 in particular), which promote stem cell self-renewal.

Asst. Prof. Kitadate said, "The lymphatic endothelial cells in the testis were described via the use of electron microscopy in the 1970s, but had scant attention paid to them for a long time. By a stroke of good luck, our screening met these cells again and threw light on their hidden roles!"

Quantitative analyses of mice with increased or decreased FGF production revealed a simple mechanism: migratory stem cells uptake and consume FGFs. Stem cells which consume more FGFs are likely to duplicate, while those that consume less are inclined to differentiate. Under this framework, stem cells effectively compete with each other for a limited supply of FGFs, leading the stem cell number to automatically adjust to a particular value, depending on the rate of FGF supply. The discovery of a novel, and extremely simple, mechanism of stem cell number control based on "competition for self-renewal promoting factors (or mitogens)" advances our understanding of the regulation of stem cells in tissues without a canonical, anatomically definable stem cell niche -- a microenvironment sometimes called an "open niche."

Prof. Simons said, "As a general and robust mechanism of stem cell density control, these findings may have important implications for the regulation of stem cell density in other tissue types."

Prof. Yoshida said, "Sperm stem cells migrate in the testis to intake FGFs, just as cows move around the meadow to eat the grass which they live on. Interestingly, the dynamics of stem cells can be described using mathematics similar to that for ecosystem -- a fruit of my beloved interdisciplinary research team!"

Date: December 20, 2018
Source: National Institutes of Natural Sciences
Summary: Researchers have revealed a novel mechanism for stem cell number control.

People with untreatable epilepsy may one day have a treatment. About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.

A team led by Ashok K. Shetty, PhD, a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, associate director of the Institute for Regenerative Medicine and a research career scientist at the Olin E. Teague Veterans' Medical Center, part of the Central Texas Veterans Health Care System, is working on a better and permanent treatment for epilepsy. Their results published this week in the Proceedings of the National Academy of Sciences (PNAS).

Seizures are caused when the excitatory neurons in the brain fire too much and inhibitory neurons -- the ones that tell the excitatory neurons to stop firing -- aren't as abundant or aren't operating at their optimal level. The main inhibitory neurotransmitter in the brain is called GABA, short for gamma-Aminobutyric acid.

Over the last decade, scientists have learned how to create induced pluripotent stem cells from ordinary adult cells, like a skin cell. These stem cells can then be coaxed to become virtually any type of cells in the body, including neurons that use GABA, called GABAergic interneurons.

"What we did is transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy," Shetty said. The hippocampus is a region in the brain where seizures originate in temporal lobe epilepsy, which is also important for learning, memory and mood. "It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy."

Further testing showed that these transplanted human neurons formed synapses, or connections, with the host excitatory neurons. "They were also positive for GABA and other markers of specialized subclasses of inhibitory interneurons, which was the goal," Shetty said. "Another fascinating aspect of this study is that transplanted human GABAergic neurons were found to be directly involved in controlling seizures, as silencing the transplanted GABAergic neurons resulted in an increased number of seizures."

"This publication by Dr. Shetty and his colleagues is a major step forward in treating otherwise incurable diseases of the brain," said Darwin J. Prockop, MD, PhD, the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine. "One important aspect of the work is that the same cells can be obtained from a patient." This type of process, called autologous transplant, is patient specific, meaning that there would be no risk of rejection of the new neurons, and the person wouldn't need anti-rejection medication.

"We will need to make sure that we're doing more good than harm," Shetty said. "Going forward, we need to make sure that all of the cells transplanted have turned into neurons, because putting undifferentiated pluripotent stem cells into the body could lead to tumors and other problems."

The development of epilepsy often happens after a head injury, which is why the Department of Defense is interested in funding the development of better treatment and prevention options.

"A great deal of research is required before patients can be safely treated," Prockop said. "But this publication shows a way in which patients can someday be treated with their own cells for the devastating effects of epilepsy but perhaps also other diseases such as Parkinsonism and Alzheimer's disease."

Shetty cautioned that these tests were early interventions after the initial brain injury induced by status epilepticus, which is a state of continuous seizures lasting more than five minutes in humans. The next step is to see if similar transplants would work for cases of chronic epilepsy, particularly drug-resistant epilepsy. "Currently, there is no effective treatment for drug-resistant epilepsy accompanying with depression, memory problems, and a death rate five to 10 times that of the general population," he said. "Our results suggest that induced pluripotent stem cell-derived GABAergic cell therapy has the promise for providing a long-lasting seizure control and relieving co-morbidities associated with epilepsy."


Date: December 20, 2018
Source: Texas A&M University
Summary: About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.

Micropores in fabricated tissues such as bone and cartilage allow nutrient and oxygen diffusion into the core, and this novel approach may eventually allow lab-grown tissue to contain blood vessels, according to a team of Penn State researchers. "One of the problems with fabrication of tissues is that we can't make them large in size," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "Cells die if nutrients and oxygen can't get inside."

Inside cells also do not differentiate if the chemical cocktail that triggers stem cells to differentiate does not reach them. A porous structure allows both nutrients and other fluids to circulate. The researchers are trying a novel approach and creating tissue building blocks with micropores. They consider this an alternative to vascularization -- growing blood vessels in the tissue -- and call the outcome porous tissue strands.

The researchers are starting with stem cells derived from human fat and mixing them with sodium alginate porogens. Derived from seaweed, sodium alginate can be printed into tiny particles that, when dissolved, leave behind tiny holes -- pores -- in the fabric of the tissue. The team uses the mixture to 3D print strands of undifferentiated tissue. They can then combine the strands to form patches of tissue.

When the researchers expose the tissue to the chemical cocktail, it turns the stem cells into specific cells, in this case bone or cartilage. Because of the pores, the fluid can flow to all of the stem cells. The researchers report in a recent issue of Biofabrication that the strands maintain 25 percent porosity and have pore connectivity of 85 percent for at least three weeks. By 3D printing strands next to and atop each other as shown in their previous work, the strands self-assemble to form patches of tissue.

"These patches can be implanted in bone or cartilage, depending on which cells they are," said Ozbolat. "They can be used for osteoarthritis, patches for plastic surgery such as the cartilage in the nasal septum, knee restoration and other bone or cartilage defects." In some ways, cartilage is easier than bone because in the human body, cartilage does not have blood vessels running through it. However, some bone is naturally porous, and so porosity is valuable in replacing or repairing that bone. While currently only tiny patches can be made, these patches are easier to fabricate than growing artificial tissue on scaffolding.

The researchers are considering applying the same methods to muscle, fat and various other tissues. Other researchers at Penn State include Yang Wu, postdoctoral fellow in engineering science and mechanics; Monika Hospodiuk, graduate student in agricultural and biological engineering; Hemanth Gudapati, graduate student in engineering science and mechanics; Thomas Neuberger, director, High Field Magnetic Resonance Imaging Facility; Srinivas Koduru, research technologist in the Department of Surgery; and Dino J. Ravnic, assistant professor of surgery, Penn State Cancer Institute. Also on the project was visiting scholar Weijie Peng, department of pharmacology, Nanchang University, China.

The National Science Foundation, the China Scholarship Council and the Jiangxi Association for Science and Technology supported this work.


Date: December 20, 2018
Source: Penn State
Summary: Micropores in fabricated tissues such as bone and cartilage allow nutrient and oxygen diffusion into the core, and this novel approach may eventually allow lab-grown tissue to contain blood vessels, according to researchers.

In mammals, generation of new neurons (neurogenesis) is mainly limited to early childhood and occurs in adulthood only in a few regions of the forebrain. One such exception is olfactory neurons, which develop from stem cells via several intermediate stages. "The production of these neurons diminishes with advancing age. In our recent study we wanted to find out the cellular basis and what role stem cells play in the process," says Dr. Carsten Marr, explaining the approach. He is a research group leader at the Institute of Computational Biology (ICB) of Helmholtz Zentrum München.

To shed light on this question, an interdisciplinary team of experts from the Helmholtz Zentrum München was formed that included the mathematicians Lisa Bast and Carsten Marr as well as stem cell researchers Dr. Filippo Calzolari (now Institute of Physiological Chemistry at the University Mainz) and Professor Jovica Ninkovic. "Our approach utilised what are known as confetti reporters to perform lineage tracing: In mouse brains, we induced individual stem cells and all their descendants -- called clones -- to light up in a specific colour," says Filippo Calzolari. In this way, the scientists could distinguish clones over time by the different colours that give the technique its name. "In the next step, we compared clones found in young and older mice to find out what contribution individual stem cells and intermediates make to the neurogenesis of mature olfactory cells," Calzolari adds.

Connect the dots

However, systematic analysis of these images proved nearly impossible for humans, in that the available data were extremely heterogeneous, making a comparison of young and old brains difficult. Here the expertise of Carsten Marr and his team came into play. They are specialists in the quantification of single-cell dynamics, i.e. the study of which and how many cells of a large population make which cell fate decisions. To do so, the researchers use artificial intelligence methods, develop mathematical models and deduce algorithms to help analyse the image data.

"We compared the confetti measurements with several mathematical models of neurogenesis," explains Lisa Bast. "We found that the ability of self-renewal declines in old age, especially in certain intermediate stages called transit amplifying progenitors." In addition, the analysis showed that asymmetric cell division and quiescence of stem cells increased in older mice. "That means that fewer cells differentiate into olfactory cells in old age as they tend to remain in the stem cell pool and become less active. Therefore, the production comes to a halt," says Jovica Ninkovic. The work is the first in which scientists have been able to quantitatively describe the behaviour of neural stem cells in the living mammalian brain using a mathematical model.


Date: December 19, 2018
Source: Helmholtz Zentrum München - German Research Center for Environmental Health
Summary: As mammals age, their sense of smell deteriorates. Scientists have now investigated why this is the case. For their study, the researchers tracked the development of stem cells in the brains of mice using what are known as confetti reporters. They then analyzed the complex data obtained using intelligent algorithms.

The discovery of pluripotent stem cells, which have the ability to differentiate into the huge range of different cell lineages that make up the human body, signaled the start of a new era in biological science and medicine. Although we are also now able to reprogram regular cells to exhibit this pluripotency, we still have much to learn about the different cues that lead such cells towards a particular cell fate, including the cells that make up the eye.

A new study reported in the journal Cell Reports has shed light on this by showing that, by growing human pluripotent stem cells on different forms of a protein called laminin, they can be induced to become corneal cells, retinal cells, and others. The cells could then be collected and used for a range of therapeutic purposes.

This study builds on earlier work by this Osaka University-centered group, which showed that exposing these stem cells to an isoform of laminin, a structural component of the matrix that fills the space outside of cells, led to the creation of cell colonies arranged as four concentric zones. Each of these zones exhibited characteristics specific to a particular anatomical component of the eye.

Here, the team grew these stem cells under conditions exclusively containing other laminin isoforms that are present in the eye, finding that this led to the creation of cells with different mobilities, densities, and tendencies to interact. They then showed that, for each particular laminin isoform, the different cells produced in the cultures matched those in different parts of the eyes of embryonic mice where the same laminin isoform predominated.

"We found that the different laminin isoforms affected whether and how fast the cells migrated outwards from the point at which the colony was originally seeded and the density at which the cells in the colony were packed," corresponding author Ryuhei Hayashi. "These different behaviors were related to the kinds of cells that the stem cells turned into, showing that we could specifically produce an ocular cell type just by choosing the appropriate type of laminin for the targeted cells."

The researchers then investigated the molecular mechanisms behind these different behaviors. They found that the form of laminin that gave rise to colonies with four concentric rings caused the contraction of extracellular structural scaffolds that tether cells together, producing higher-density colony centers. This in turn led to the inactivation of a protein called YAP, which promoted the differentiation into retinal-like cells in the colony centers.

"Now that we can use different laminins to program stem cells to become particular cells found in different parts of the eye, we can harvest and apply them in treatments for a range of ocular diseases," last author Kohji Nishida says. "This could be an extremely useful tool in the field of ophthalmology."

Date: December 19, 2018
Source: Osaka University
Summary: Researchers revealed that culturing human induced pluripotent stem cells with different isoforms of the extracellular component laminin led to the creation of cells specific to different parts of the eye, including retinal, corneal, and neural crest cells. They showed that the different laminin variants affected the cells' motility, density, and interactions, resulting in their differentiation into specific ocular cell lineages. Cells cultured in this way could be used to treat various ocular diseases.

Scientists identified two distinct control mechanisms in the developmental transition of undifferentiated stem cells into healthy brain cells. This fundamental research using mice may inform regenerative medicine treatments for neurodegenerative diseases and spinal cord injuries, in the future.

When an embryo develops, stem cells differentiate into all the types of cells that the adult will need. Neural stem cells differentiate first into neurons, or nerve cells, and then into astrocytes, support cells in the brain. Neural stem cells lose their potential to produce neurons as the embryo matures. Professor Yukiko Gotoh at the University of Tokyo leads the team of scientists who identified the epigenetic control mechanisms of how neural stem cells lose the potential to produce neurons.

"It is a paradox for regenerative medicine that neural stem cells produce fewer cells as they differentiate into additional cell types. We would like to grow specific cell types and lots of them," said Gotoh. All body cells have the same DNA, but different genes are turned on or off to make different cell types. To understand brain development, researchers examined how a protein called polycomb repressive complex 1 (PRC1) controls the expression of genes related to neuronal function inside neural stem cells. Earlier results had revealed PRC1 regulates gene expression in stem cells, but not the specifics how and when.

They collected neural stem cells from the brains of mouse embryos that grew inside a mother mouse until the midpoint of the embryonic development period, or 11 days after conception. Then, researchers separated the cells into two groups to grow outside the body for different periods: one group until it reached the early stage of neural development, when neurons are formed, and the other group until the late stage when the cells turn into astrocytes.

"Neural stem cells must keep track of their own calendar. Even while growing outside the body they differentiate normally into neurons and then into astrocytes," said Gotoh. Researchers discovered that PRC1 represses genes related to neuronal function through activity of adding a molecule called ubiquitin during early stages of brain development in which neural stem cells produce neurons. Then, at later stages of brain development when stem cells switch to producing astrocytes, the ubiquitin-adding activity becomes unnecessary. PRC1 instead becomes clusters (polymers) on these genes in the late stage.

PRC1 represses genes related to neuronal function transiently in the early stage, but permanently in the late stage of brain development. Understanding the different control mechanisms at two distinct stages of brain development may provide researchers with new tools to manipulate neural stem cells. The results may also help develop methods to change a cell's type: for example, collecting astrocytes out of adult patients and turning those cells into new neurons.

Understanding how the brain first develops different cell types helps researchers imagine how to design treatments for neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), when those cells are damaged. Scientists could also use the same information to treat neuron damage elsewhere in the body, including spinal cord injuries and other ailments.

Date: December 18, 2018
Source: University of Tokyo
Summary: Scientists identified two distinct control mechanisms in the developmental transition of undifferentiated stem cells into healthy brain cells. This fundamental research using mice may inform regenerative medicine treatments for neurodegenerative diseases and spinal cord injuries, in the future.

Insulin is secreted from the beta cells which are located in the pancreas, and it is crucial for the maintenance of normal blood sugar levels. Deficiency of insulin leads to diabetes, characterized by elevated blood sugar. Diabetes most commonly presents in childhood as Type 1 diabetes and in adults as Type 2 diabetes.

Sometimes diabetes is diagnosed already in very small babies, during the first six months of life. In these cases, mutations in the gene encoding insulin are often found. These mutations are only found in one copy of the gene; that means that half of the produced insulin is normal, which should be enough to secure normal blood sugar. However, this is not the case: insulin secretion stops totally after a few months. It is believed that this is caused by a toxic effect of the mutant insulin inside the cell, but the exact mechanisms are poorly understood.

Mutant insulin is known to cause a chronic stress reaction in the beta cell, and it has been thought that this leads to the death of the cell. It is important to understand the detailed consequences of beta-cell stress, because this may help to develop drugs for the prevention of both rare and common forms of diabetes. "We now had the chance to test this with real patient-derived cells," tells Professor Timo Otonkoski from the University of Helsinki.

Researchers created a human disease model using stem cells from people carrying insulin gene mutations; then they corrected cells using a gene editing technique called CRISPR. The mutant and corrected stem cells were then induced to turn into insulin-secreting beta cells and the researchers followed the function of the cells after transplanting them in mice.

"The main finding of the study was that these cells do not die from the chronic stress, but their growth and development is disturbed. These effects are mediated through processes that could potentially be targeted by drugs," Dr. Diego Balboa says.

"In this study, we describe mechanisms linking chronic cellular stress to the poor development of the insulin-producing cells. A strongly reduced number of beta-cells will cause diabetes immediately, but even a milder defect will increase the risk of diabetes later in life. Understanding the molecular mechanisms of these processes may help in devising ways to preserve the mass and function of beta cells," Otonkoski states.

Date: December 17, 2018
Source: University of Helsinki
Summary: Researchers have described mechanisms linking chronic cellular stress to the poor development of the insulin-producing cells.

New study shows how newly created cardiac muscle cells can be made to pump together. A team of Rutgers scientists, including Leonard Lee and Shaohua Li, have taken an important step toward the goal of making diseased hearts heal themselves -- a new model that would reduce the need for bypass surgery, heart transplants or artificial pumping devices. The study, recently published in Frontiers in Cell and Developmental Biology, involved removing connective tissue cells from a human heart, "reverse-engineering" them into heart stem cells, then "re-engineering" them into heart muscle cells.

The Rutgers team's true breakthrough, however, is that the newly created cardiac muscle cells clumped together into a single unit that visibly pumps under the microscope. Senior author Leonard Y. Lee, chair of the Department of Surgery at Rutgers Robert Wood Johnson Medical School, said cardiac cells made in this way don't normally come together and beat as one. His team succeeded in making this happen by over-expressing, a protein in the cells called CREG.

According to Lee, fibroblasts, a cell in connective tissue, were isolated from the heart tissue and reverse-engineered -- or transformed -- into stem cells. This was done so that when the CREG protein was over expressed the stem cells would differentiate into cardiac cells. "Heart failure has reached epidemic proportions. Right now, the only option to treat it is surgery, transplant, or connecting the patient with a blood-pumping machine," Lee said. "But transplantable hearts are in short supply and mechanical devices limit the patient's quality of life. So, we are working for ways to help hearts heal themselves."

Though still far off, Lee's ultimate goal is to be able to remove small amounts of a patient's native heart tissue, use CREG to convert the tissue into cardiac muscles that will work together cohesively, and re-introduce them into the patient's heart allowing it to heal itself. More than six million Americans are living with heart failure, according to the American Heart Association. While most people hear the term "heart failure" and think this means the heart is no longer working at all, but it actually means that the heart is not pumping as well as it should be. People with heart failure often experience fatigue and shortness of breath and have difficulty with every day activities such as walking and climbing stairs.

Date: December 14, 2018
Source: Rutgers University
Summary: Scientists have taken an important step toward the goal of making diseased hearts heal themselves -- a new model that would reduce the need for bypass surgery, heart transplants or artificial pumping devices.

NK cells, or natural killer cells, play an important role in the body's defences against cancer and various infections. Now, in a joint project, researchers at Lund University in Sweden, the University of Oxford and Karolinska Institutet in Stockholm have mapped how the different steps of the maturation process of these supercells from blood producing stem cells in the bone marrow are regulated: knowledge which is crucial for the development of new immunotherapies against cancer.

Within the immune system, NK cells act as the front line of the body's defences: they can recognise and kill cancer cells as well as cells infected by viruses. Because of this important function, many current studies focus on investigating how NK cells could be used as a basis for immunotherapy against cancer. Whereas T lymphocytes and B lymphocytes -- two other important players in the immune system that also develop from blood stem cells are well studied, the maturation process of NK cells is less understood.

"In order to fully utilise NK cell properties in cell based therapy, we first need to understand how these supercells are produced. What is a developmental map from a blood stem cell to a fully mature functional cell within the immune system and how it is regulated? We therefore wanted to learn more about how NK cells are generated and what mechanisms control their development and function," explains Ewa Sitnicka, the Lund University professor who led the study now published in the Journal of Immunology. In her research, she studies how stem cells differentiate and produce different types of lymphocytes.

Signal pathway crucial to function and maturation

Notch proteins are a family of receptors in a highly conserved cell communication system. Notch signalling controls cell development both in animals and humans. The researchers investigated what happens when the signals generated through activation of Notch proteins are shut down. They found that Notch signalling is necessary for NK cells to develop and function normally. When the researchers studied the mouse model where the Notch function has been inactivated in the blood cells, they found that the NK cells were reduced in numbers and their function was affected.

"Without Notch signalling, the NK cells did not mature normally and their numbers were reduced. This could be significant for the NK cells' ability to fight cancer and infections," explains Ewa Sitnicka. The new knowledge will help us to better understand how to generate NK cells for their use in immunotherapy.

Date: December 13, 2018
Source: Lund University
Summary: NK cells, or natural killer cells, play an important role in the body's defences against cancer and various infections. Now scientists have mapped how the different steps of the maturation process of these supercells from blood producing stem cells in the bone marrow are regulated: knowledge which is crucial for the development of new immunotherapies against cancer.