Author Archives: admin


New insight into how immune cells are formed – Medical Xpress

August 10, 2017

In contrast to what has been previously believed, development of blood stem cells into mast cells, a type of specialised immune cell, does not depend on stem cell factor. This has been demonstrated in a new collaborative study by researchers at Karolinska Institutet and Uppsala University, and published in the scientific journal Blood. The results could pave the way for new treatments for certain types of blood diseases.

Allergy and asthma affect a high percentage of the population. Mast cells are specialised immune cells that play an important role not only in these conditions but also in other diseases such as mastocytosis, a haematologic disease involving an increased number of mast cells. It has been commonly understood that the growth factor stem cell factor, which stimulates mast cell development, is essential for the formation of mast cells. Now researchers at Karolinska Institutet and Uppsala University have shown that this is not the case. The researchers analysed mast cells and their progenitors in blood from patients with chronic myeloid leukaemia, a disease of the blood.

"When the patients were treated with the drug imatinib (Glivec), which blocks the effect of stem cell factor, the number of mature mast cells dropped, while the number of progenitor cells did not change. We were thus able to conclude that mast cell progenitors did not require stem cell factor", says Professor Gunnar Nilsson at the Department of Medicine, Solna, and the Centre of Excellence for Systemic Mastocytosis at Karolinska Institutet, and visiting professor at the Department of Medical Sciences, Uppsala University, who led the study.

By culturing the mast cell progenitor cells present in blood, which are relatively uncommon (about 10 cells per million white blood cells), the researchers found that mast cell progenitors could survive, divide and partially mature without stem cell factor. Instead, development can take place with the factors interleukin 3 and 6.

"The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example for mastocytosis for which treatment with imatinib/Glivec is not effective. One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases", comments Joakim Dahlin, researcher at the Department of Medicine, Solna, at Karolinska Institutet and first author of the study.

Explore further: Proof-of principle study finds imatinib improves symptoms for patients with severe asthma

More information: Joakim S. Dahlin et al. KIT signaling is dispensable for human mast cell progenitor development, Blood (2017). DOI: 10.1182/blood-2017-03-773374

Journal reference: Blood

Provided by: Uppsala University

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Continue reading here:
New insight into how immune cells are formed - Medical Xpress

Microchip May Fix Damaged Cells And Organs, Scientists Say – CBS New York

August 8, 2017 6:48 PM

COLUMBUS, Ohio (CBSNewYork) It sounds like something out of a sci-fi novel a microchip that rescues injured or failing organs.

As CBS2s Dr. Max Gomez reported Tuesday, the breakthrough in regenerative medicine is actually being tested right now.

One of the hottest areas of medical research is using cells instead of drugs to treat diseases and injuries. But cellular therapies require finding or making the right type of cells, which can be difficult.

It turns out the body can do it on its own, with a little high-tech help.

The device is only about the size of a cufflink, but what it could represent is enormous. In a laboratory at the Ohio State University Wexner Medical Center, researchers demonstrated how it reprograms cells.

The chip is simply placed on an injured part of the body and a small electrical current is applied.

This process only takes less than a second and is non-invasive and then youre off, said Dr. Chan of Ohio State Wexner Medical Center. The chip does not stay with you, and the reprogramming of the cell starts.

That reprogramming turns skin cells into nearly any type of cell doctors might need to treat a patient a breakthrough technology in regenerative medicine.

For example, in a leg that is badly injured and lacks blood flow, doctors simply touch the chip to the leg and reprogram the skin to become functioning blood vessels.

And it will quickly shoot the DNA right into the cells, said Dr. James Lee of the Ohio State College of Engineering.

In many cases in seven days, you start seeing changes and these changes to our pleasant surprise persists, Dr. Sen said.

Within a week, there are active blood vessels and by the second week, the leg is saved.

It is important to note that the procedure has not yet been tested in humans. But after developing the concept, researchers were determined to test it in real life.

So we tried them on the mouse and put it on the skin, and you know what? It actually works, said Dr. James Lee of the Ohio State College of Engineering. It affects the entire tissue, not just the surface.

An image shows the mouses leg is injured, and vascular scans show there is little blood flow. But after one touch with the chip, in just three weeks, the blood flow was back and the injured leg was saved.

Our technology is not just limited to be used on the skin, Dr. Sen said. It can be used in other tissues within the body or outside the body, so on and so forth. So, skin is only one example.

In fact, in lab tests the chip even worked in the brain helping mice recover from strokes. In humans, it could allow doctors to grow brain cells on a persons skin under the guidance of their own immune system.

They could then harvest the cells and inject them into the brain to treat conditions such as Alzheimers disease and Parkinsons disease without any immune suppression drugs being necessary.

The electrical current actually opens up channels in the skin cells that allow the delivery of factors that are known to change the expression of certain genes in those cells. Better yet, the reprogramming doesnt have to be in a hospital setting because there is nothing invasive about it.

Follow this link:
Microchip May Fix Damaged Cells And Organs, Scientists Say - CBS New York

Researchers use CRISPR to manipulate social behavior in ants – Phys.Org

August 10, 2017 This photograph shows Ooceraea biroi workers tagged with color dots for individual behavioral tracking. Credit: Daniel Kronauer The Rockefeller University

The gene-editing technology called CRISPR has revolutionized the way that the function of genes is studied. So far, CRISPR has been widely used to precisely modify single-celled organisms and, more importantly, specific types of cells within more complex organisms. Now, two independent teams of investigators are reporting that CRISPR has been used to manipulate ant eggsleading to germline changes that occur in every cell of the adult animals throughout the entire ant colony. The papers appear August 10 in Cell.

"These studies are proof of principle that you can do genetics in ants," says Daniel Kronauer, an assistant professor at The Rockefeller University and senior author of one of the studies. "If you're interested in studying social behaviors and their genetic basis, ants are a good system. Now, we can knock out any gene that we think will influence social behavior and see its effects."

Because they live in colonies that function like superorganisms, ants are also a valuable model for studying complex biological systems. But ant colonies have been difficult to grow and study in the lab because of the complexity of their life cycles.

The teams found a way to work around that, using two different species of ants. The Rockefeller team employed a species called clonal raider ants (Ooceraea biroi), which lacks queens in their colonies. Instead, single unfertilized eggs develop as clones, creating large numbers of ants that are genetically identical through parthogenesis. "This means that by using CRISPR to modify single eggs, we can quickly grow up colonies containing the gene mutation we want to study," Kronauer says.

The other team, a collaboration between researchers at New York University and the NYU School of Medicine, Arizona State University, the Perelman School of Medicine at the University of Pennsylvania, and Vanderbilt University. , used Indian jumping ants (Harpegnathos saltator). "We chose this species because they have a peculiar feature that makes it easy to transform workers into queens," says Claude Desplan, a Silver Professor at NYU and one of the senior authors of the second study. If the queen dies, the young worker ants will begin dueling for dominance. Eventually, one of them becomes a "pseudoqueen"also called a gamergateand is allowed to lay eggs.

"In the lab, we can inject any worker embryo to change its genetic makeup," Desplan says. "We then convert the worker to a pseudoqueen, which can lay eggs, propagate the new genes, and spawn a new colony."

Desplan, co-senior author Danny Reinberg, a Howard Hughes Medical Institute investigator at NYU Langone, and Shelley Berger, the Daniel S. Och University Professor in the departments of Cell and Developmental Biology and Biology at Penn, began studying these ants several years ago as a way to learn about epigenetics, which refers to changes in gene expression rather than changes in the genetic code itself. "The queens and the worker ants are genetically identical, essentially twin sisters, but they develop very differently," Desplan says. "That makes them a good system for studying epigenetic control of development."

The gene that both research teams knocked out with CRISPR is called orco (odorant receptor coreceptor). Ants have 350 genes for odorant receptors, a prohibitively large number to manage individually. But due to the unique biology of how the receptors worka great stroke of luck, in this casethe investigators were able to block the function of all 350 with a single knockout. "Every one of these receptors needs to team up with the Orco coreceptor in order to be effective," says Waring Trible, a student in Kronauer's lab and the first author of the Rockefeller study.Once the gene was knocked out, the ants were effectively blind to the pheromone signals they normally use to communicate. Without those chemical cues, they become asocial, wandering out of the nest and failing to hunt for food.

More surprisingly, knocking out orco also affected the brain anatomy in the adult animals of both species. In the same way that humans have specialized processing centers in the brain for things like language and facial recognition, ants have centers that are responsible for perceiving and processing olfactory cues that are expanded compared to other insects. But in these ants, the substructures of these sensory centers, called the antennal lobe glomeruli, were largely missing.

"There are many things we still don't know about why this is the case," Kronauer says. "We don't know if the neurons die back in the adults because they're not being used, or if they never develop in the first place. This is something we need to follow up on. And eventually, we'd like to learn to what extent the phenomenon in ants is similar to what's going on in mammals, where brain development does depend to a large extent on sensory input."

"Better understanding, biochemically speaking, how behavior is shaped could reveal insights into disorders in which changes in social communication are a hallmark, such as schizophrenia or depression," Berger says.

In a third related study from the University of Pennsylvania, researchers led by Roberto Bonasio altered ant behavior usingthe brain chemical corazonin. When corazonin is injected into ants transitioning to become a pseudo-queen, it suppresses expression of thebrain protein vitellogenin. This change stimulated worker-like hunting behaviors, while inhibiting pseudo-queen behaviors, such as dueling and egg deposition.

The video will load shortly.

Further, when the team analyzed proteins the ant brain makes during the transition to becoming a pseudo-queen, they found that corazonin is similar to a reproductive hormone in vertebrates. More importantly, they also discovered that release of corazonin gets turned off as workers became pseudo-queens. Corazonin is also preferentially expressed in workers and foragers from other social insect species. In addition to corazonin, several other genes were expressed in a worker-specific or queen-specific way.

"Social insects such as ants are outstanding models to study how gene regulation affects behavior," says Bonasia, an assistant professor of Cell and Developmental Biology. "This is because they live in colonies comprised of individuals with the same genomes but vastly different sets of behaviors."

Explore further: 'Princess pheromone' tells ants which larvae are destined to be queens

More information: 1. Cell, Trible et al: "orco mutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants." http://www.cell.com/cell/fulltext/S0092-8674(17)30772-9 , DOI: 10.1016/j.cell.2017.07.001

2. Cell, Yan et al: "An engineered orco mutation produces aberrant social behavior and defective neural development in ants" http://www.cell.com/cell/fulltext/S0092-8674(17)30770-5 , DOI: 10.1016/j.cell.2017.06.051

3. Cell, Gospocic et al.: "The neuropeptide corazonin controls social behavior and caste identity in ants" http://www.cell.com/cell/fulltext/S0092-8674(17)30821-8 , DOI: 10.1016/j.cell.2017.07.014

Journal reference: Cell

Provided by: Cell Press

For Indian jumping ants (Harpegnathos saltator), becoming royalty is all about timing.

Imagine working for the harshest corporation in the world.

It's a waxy layer that covers their bodies and is the source of the complex aromas that ants use to communicate. These odorant blends act like biochemical uniforms, identifying individual ants by caste, colony and species. ...

Scientists have finally sequenced the entire genome of an ant, actually two very different species of ant, and the insights gleaned from their genetic blueprints are already yielding tantalizing clues to the extraordinary ...

NYU School of Medicine researcher Dr. Danny Reinberg was awarded a Howard Hughes Institute of Medicine Collaborative Innovation Award for new research on ant epigenetics- helping to unravel the impact lifestyle and environment ...

Queen and worker ants develop from the same sets of genes, but perform completely different ecological roles. How the same genes result in two types of individuals is an ongoing mystery. In the past, scientists have only ...

The gene-editing technology called CRISPR has revolutionized the way that the function of genes is studied. So far, CRISPR has been widely used to precisely modify single-celled organisms and, more importantly, specific types ...

In the cells of palm trees, humans, and some single-celled microorganisms, DNA gets bent the same way. Now, by studying the 3-D structure of proteins bound to DNA in microbes called Archaea, University of Colorado Boulder ...

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the current issue of Science, Nikolaus Rajewsky and his team at the ...

Until recently, the CRISPR-Cas9 gene editing technique could only be used to manipulate DNA. In a 2016 study, University of California San Diego School of Medicine researchers repurposed the technique to track RNA in live ...

Researchers studying turtle-headed seasnakes living on coral reefs in the Indo-Pacific noticed something unusual about the snakes' color patterns: seasnakes living in more pristine parts of the reef were decorated with black-and-white ...

Chimpanzees of all ages and all sexes can learn the simple circular relationship between the three different hand signals used in the well-known game rock-paper-scissors. Even though it might take them longer, they are indeed ...

Adjust slider to filter visible comments by rank

Display comments: newest first

Does this mean that we are only a few years away from being able to cure homosexuality?

Do you want mutant ants? Because that's how you get mutant ants!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

More:
Researchers use CRISPR to manipulate social behavior in ants - Phys.Org

Method offers better conditions for studying insulin-producing cells – Medical Xpress


Medical Xpress
Method offers better conditions for studying insulin-producing cells
Medical Xpress
Researchers have established a unique method enabling them to study the function of insulin-producing cells under conditions that are similar to those in humans. This can pave the way to development of new medicines for the treatment of diabetes.

More here:
Method offers better conditions for studying insulin-producing cells - Medical Xpress

Center For Cell & Gene Therapy – Cell Therapy

1102 Bates Street, Suite 1670

Houston, Texas 77030

The GMP Facilities at the Center for Cell and Gene Therapy at Baylor College of Medicine are among the largest and most modern in the United States. Manufacturing of therapeutic biologics has existed at Baylor for more than twenty years, and is now centralized in 19,000 square feet on the 16th floor of the Feigin Center at Texas Childrens Hospital.

This facility opened in 2010 and contains 22 ISO 7 clean room suites supported by dedicated space for cell and product cold storage, flow cytometric analysis, quality control testing, data management and storage and quality assurance activities. The staff has extensive experience in GMP manufacturing of a wide variety of products and intermediates for cellular therapies and of viral and non-viral vectors, and master and working cell banks.

Manufacturing and testing supports more than 30 investigator-sponsored INDs conducted at the Texas Medical Center and institutions around the United States. Products have also been prepared under contract for researchers in Europe, Asia and Australia. The range of products that have been manufactured is shown under the Vector and Cell Therapy Facilitypages.

The facility is also accredited by the Foundation for the Accreditation of Cellular Therapy (FACT)and is CLIA registered for high complexity testing.

Center for Cell & Gene Therapy - cGMP Facilities

See the article here:
Center For Cell & Gene Therapy - Cell Therapy

VAX-DC/MM Cell Therapy Shows Promise in Relapsed or Refractory Myeloma, Lymphoma Patients – Myeloma Research News

NantKwests Vax-DC/MM cell therapy has induced a partial or complete response in 42 percent ofrelapsed or refractory multiple myeloma (MM) and lymphoma patients in a Phase 1 clinical trial (NCT02248402). The findings showed no evidence of severe adverse events.

Results of this work were published under the title A phase I clinical study of autologous dendritic cell therapy in patients with relapsed or refractory multiple myeloma in the journal Oncotarget.

Natural killer (NK) cells, the bodys first line of defense, have the innate ability to rapidly seek and destroy abnormal cells, like cancer cells, without requiring prior exposure or activation by support molecules. They also are able to activate more specific immune cells, likeB-cells and T-cells, against a particular target.

NantKwests cell therapy, VAX-DC/MM, uses transplants of dendritic cells (another immune cell type) to improve the action of NK cells. The dendritic cells, extracted from the blood of myeloma patients, were incubated with inactive myeloma cells, which rendered them specific to target such cells.

In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM, the researchers wrote.

The trial enrolled 12 patients who previously had been treated with both thalidomide- and bortezomib-based therapies. Participants received a median of five prior treatment regimens, and had been diagnosed for a median of 56.6 months.

All patients underwent VAX-DC/MM therapy once everyfour weeks. Three patients were treated with five cells, and three patients were treated with 10 million cells. After the higher dose was established as the tolerable dose, an additional six patients received the 10 million cell dose.

Results showed that VAX-DC therapy had a clinical benefit rate of 66.7 percent: One patient (11.1%) had a minor response to treatment, five (55.6%) had stable disease, and three (33.3%) saw their tumor progress. Importantly, one patient with relapsed Hodgkin lymphoma and one with myeloma had a complete response, and have remained disease-free after 10 and two years, respectively.

Our study was designed to assess safety and preliminary evidence of efficacy in patients with relapsed, refractory hematological malignancies whose disease recurred after autologous hematopoietic cell transplantation (AHCT), Armand Keating, MD, said in a press release. Keating is director of the Cell Therapy program at the Princess Margaret Cancer Centre and University Health Network.In this heavily pretreated patient population that has a particularly poor prognosis, we demonstrated safety with minimal toxicity and showed preliminary evidence of efficacy, taking advantage of the unique properties of natural killer (NK) cells as an immuno-therapeutic agent, she said.

VAX-DC therapy was well-tolerated, and the most frequent adverse events were local reactions at the injection site and infusion-related reactions.

In this clinical study completed in 2015 of 12 patients with lymphoma and multiple myeloma who had relapsed after AHCT for refractory/relapsed disease, we report encouraging results said Keating, leading her to conclude that aNK cell therapy warrants further clinical investigation.

Consistent with previous studies, Dr. Keatings clinical trial results, reporting a 42% overall response rate, provide additional clinical validation of the unique potential to deliver long-term remissions with limited toxicity using the companys novel NK cell therapy, said Patrick Soon-Shiong, NantKwests chairman and CEO.

Read the original here:
VAX-DC/MM Cell Therapy Shows Promise in Relapsed or Refractory Myeloma, Lymphoma Patients - Myeloma Research News

Is stem cell injection the cure-all miracle? – Health24

08 August 2017 Stem cells are not only used in cancer treatment, but may be effective for a variety of other conditions.

Stem cell therapy has been claimed to cure cancer, improve chronic conditions such as headaches, and even make your skin look younger. How can that not be a good thing?

Youve probably heard about stem cell research before, but what exactly are stem cells, and how can stem cells injected into the body treat various diseases and conditions?

There has been enormous progress in this field over the last few decades, so let's take a look at how stem cell injections work.

What exactly are stem cells?

Stem cells are the bodys building blocks the reserve cells that the body is made up of. These cells are able to produce multiple different cells, each performing a specific function. Stem cells can be divided into two main categories:

What is stem cell therapy?

Stem cell therapy can be categorised as regenerative medicine. Stem cells used in medical treatments are currently harvested from three sources: umbilical cord blood, bone marrow and blood. These are treatments that restore damaged tissue and regenerate new cells in the case of illness or injury.

While there are other forms of stem cell therapy, these are still in the early stages and regarded as research.

How is stem cell therapy performed?

Adult stem cells are derived from a blood sample and injected back into the patient's blood. The surrounding cells are then activated, stimulating rejuvenation in the area.

Why the controversy?

In 2004 South Africa became the first African nation to open a stem cell bank. This involved embryonic stem cells for cloning research and not the "adult" stem cells used in treatment.

Embryonic stem cells are often viewed as problematic, as they are derived from very young foetuses. It is thus viewed as a form of "abortion" to use embryonic stem cells for treatment. But in most cases of stem cell therapy adult stem cells are used, which causes few ethical problems. Stem cells derived from the umbilical cord are not the same as from the embryo.

What does science say?

Prof Jacqui Greenberg from the University of Cape Town stated that although stem cells can potentially treat various diseases, they should be treated with extreme care.

She has no doubt that in time (in medical science particularly, progress is slow and measured in blocks of 10 years), stem cells will be the solution for many things. "But right now we have to strike a balance of not creating too much hype and raising hope too soon. Stem cells are the future, but the future is not now," Greenberg states.

The reason for this is that stem cells derived from an adult are too volatile at times. Researchers are not clear on how many of these stem cells will actually "survive" and "activate" to treat the condition at hand. Therefore it can't be predicted how many cells will survive and become functional.

There is as yet little proof that stem cells can actually fight disease when injected back into the host.Despite the success of IPS cell technology up to date, there are stillchallenges with regard to the purity of stem cells before their use in therapy.

Availability and cost in South Africa

Stem cell therapy is available at various treatment centres in South Africa. One of the most prominent is the South African Stem Cell Institute in the Free State. Here, various treatments, such as regenerative skin treatments and prolotherapy (regeneration of the joints), are offered.

Therapy starts with an initial consultation. During the second consultation vitals are checked, followed by either the fat harvest procedure under tumescent anaesthesia or bone marrow aspiration under local anaesthesia.

The stem cells are then cryopreserved and injected into the patient as needed. Prices of the treatment vary from R500 (for a once-off treatment in a small area, such as the hand) to R22 500 (a comprehensive process), depending on the condition being treated and length of treatment needed. This excludes the initial consultation fee and after-care.

There are also stem cell banks in South Africa, such as Cryo-Save, where stem cells can be stored at an annual fee (excluding initial consultation, testing and harvesting) and used for treatment.

Do your own research

If you do want to go the stem cell route, make sure that the medical programme being offered is legitimate and that the projected outcome is based on real evidence.

There are a number of private institutions banking on the promise of curing any number of diseases with stem cells from a patient's own blood. The truth, however, is that there is no conclusive proof that the majority of these diseases can be cured with the person's own stem cells annihilating the claim that stem cell therapy is the solution to all diseases.

The rest is here:
Is stem cell injection the cure-all miracle? - Health24

How Food Preservatives May Disrupt Human Hormones – Laboratory Equipment

Can chemicals that are added to breakfast cereals and other everyday products make you obese? Growing evidence from animal experiments suggests the answer may be "yes." But confirming these findings in humans has faced formidable obstacles - until now.

A new study published today in Nature Communications details how Cedars-Sinai investigators developed a novel platform and protocol for testing the effects of chemicals known as endocrine disruptors on humans.

The three chemicals tested in this study are abundant in modern life. Butylhydroxytoluene (BHT) is an antioxidant commonly added to breakfast cereals and other foods to protect nutrients and keep fats from turning rancid; perfluorooctanoic acid (PFOA) is a polymer found in some cookware, carpeting and other products; and tributyltin (TBT) is a compound in paints that can make its way into water and accumulate in seafood.

The investigators used hormone-producing tissues grown from human stem cells to demonstrate how chronic exposure to these chemicals can interfere with signals sent from the digestive system to the brain that let people know when they are "full" during meals. When this signaling system breaks down, people often may continue eating, causing them to gain weight.

"We discovered that each of these chemicals damaged hormones that communicate between the gut and the brain," said Dhruv Sareen, PhD, assistant professor of Biomedical Sciences and director of the Induced Pluripotent Stem Cell Core Facility at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "When we tested the three together, the combined stress was more robust."

Of the three chemicals tested, BHT produced some of the strongest detrimental effects, Sareen said.

While other scientists have shown these compounds can disrupt hormone systems in laboratory animals, the new study is the first to use human pluripotent stem cells and tissues to document how the compounds may disrupt hormones that are critical to gut-to-brain signaling and preventing obesity in people, Sareen said.

"This is a landmark study that substantially improves our understanding of how endocrine disruptors may damage human hormonal systems and contribute to the obesity epidemic in the U.S.," said Clive Svendsen, PhD, director of the institute and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine. More than one-third of U.S. adults are considered to be obese, according to federal statistics.

The new testing system developed for the study has the potential to provide a much-needed, safe and cost-effective method that can be used to evaluate the health effects of thousands of existing and new chemicals in the environment, the investigators say.

For their experiments, Sareen and his team first obtained blood samples from adults, and then, by introducing reprogramming genes, converted the cells into induced pluripotent stem cells. Then, using these stem cells, the investigators grew human epithelium tissue, which lines the gut, and neuronal tissues of the brain's hypothalamus region, which regulates appetite and metabolism.

The investigators then exposed the tissues to BHT, PFOA and TBT, one by one and also in combination, and observed what happened inside the cells. They found that the chemicals disrupted networks that prepare signaling hormones to maintain their structure and be transported out of the cells, thus making them ineffective. The chemicals also damaged mitochondria - cellular structures that convert food and oxygen into energy and drive the body's metabolism.

Because the chemical damage occurred in early-stage "young" cells, the findings suggest that a defective hormone system potentially could impact a pregnant mother as well as her fetus in the womb, Sareen said. While other scientists have found, in animal studies, that effects of endocrine disruptors can be passed down to future generations, this process has not been proved to occur in humans, he explained.

More than 80,000 chemicals are registered for use in the U.S. in everyday items such as foods, personal care products, household cleaners and lawn-care products, according to the National Toxicology Program of the U.S. Department of Health and Human Services. While the program states on its website that relatively few chemicals are thought to pose a significant risk to human health, it also states: "We do not know the effects of many of these chemicals on our health."

Cost and ethical issues, including the health risk of exposing human subjects to possibly harmful substances, are among the barriers to testing the safety of many chemicals. As a result, numerous widely used compounds remain unevaluated in humans for their health effects, especially to the hormone system.

"By testing these chemicals on actual human tissues in the lab, we potentially could make these evaluations easier to conduct and more cost-effective," Sareen said.

Read more from the original source:
How Food Preservatives May Disrupt Human Hormones - Laboratory Equipment

Novel stem cell-derived model created of inflammatory neurological disorder – Medical Xpress

August 10, 2017 Organoids are clusters of cultured cells self-organized into miniature replicas of organs. In this image, neural progenitor cells (NPCs) are green. As the brain organoids increase in size, multi-layer structures composed of NPCs develop with intermediate progenitors (not shown) and cortical layer neurons (red). Cell nuclei are depicted in blue. Credit: Cleber A. Trujillo, UC San Diego

An international team of scientists, led by University of California San Diego School of Medicine researchers, has created a human stem cell-based model of a rare, but devastating, inherited neurological autoimmune condition called Aicardi-Goutieres Syndrome (AGS). In doing so, the team was able to identify unusual and surprising underlying genetic mechanisms that drive AGS and test strategies to inhibit the condition using existing drugs.

Two repurposed FDA-approved drugs showed measurable effect, rescuing cells from the effects of AGS. The findings point to the promise of future clinical trials and to the utility of creating novel stem cell-based models of human diseases when no other models are available.

The findings are published in the August 10 online issue of Cell Stem Cell.

"Our approach can now be used to investigate other neurological conditions, like autism and schizophrenia and overlapping autoimmune disorders that dysfunction in similar ways," said Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.

First described in 1984, AGS typically involves early-onset inflammation affecting the brain, immune system and skin. Its severity depends upon which genes are involvedthere are six typesbut usually results in pronounced physiological and psychological consequences, from microcephaly (an abnormally small head) and spasticity to skin and vision problems and joint stiffness, all appearing in the first year of life. The syndrome is progressive, resulting in death or a persistent vegetative state in early childhood. Currently, there is no cure; the only treatments are symptomatic or palliative.

The clinical features of AGS mimic those of viral infections acquired in utero, before birth, with increased levels of inflammatory markers and other signatures of inflammatory response. However, Muotri said there is no link between AGS and exogenous pathogens. Previous research has shown that AGS patients have mutations in genes critical to nucleic acid metabolism in the regulation of cellular immune response, among them a deficiency in an enzyme called TREX1, which helps prevent abnormal DNA from accumulating in cells.

Deeper probing into the pathogenesis of AGS has been difficult because animal models do not accurately mimic the human version of the disease. So Muotri, with colleagues, used embryonic stem cells and induced pluripotent stem cells (iPSCs) derived from AGS patients to create six cellular models of the condition. In the past, Muotri's lab has developed similar "disease-in-a-dish" neuronal models of autism, anorexia nervosa and Williams Syndrome, among other rare genetic neurological conditions.

From the iPSCs, they also created cerebral organoids or "mini-brains"larger clusters of neurons that organize themselves into a cortical structure, similar to a developing human cerebral cortex.

The researchers found that with TREX1 not functioning normally, all of the cell models displayed excess extra-chromosomal DNA and that a major source of the excess DNA came from LINE1 (L1) retroelements. L1s are repetitive sequences of DNA with the ability to autonomously copy-and-paste themselves within the human genome. In the past, they have been called "jumping genes" and, because their function within cells is largely unknown, "junk DNA."

However the term "junk DNA" is increasingly becoming a misnomer. In work published in 2005, for example, Muotri and colleagues reported that L1s have a high impact on brain cells compared to other tissues, suggesting an important, if so far mysterious, role in brain development.

Since then, he said, researchers around the world have investigated the role of L1s in creating a genetic mosaicism in the brain. "These are ancient, genomic parasites that replicate inside our cells. The majority of the current work is focusing on the impact of this genome mosaicism, but we decided to also look outside of the nucleus. And what we found was a big surprise."

In some of the AGS cell models created by the researchers, toxins from excess DNA built up. Others showed an abnormal immune response, secreting toxins that induced cell death in other cells. The combined effect in organoids was a massive reduction in neuron growth when the opposite should occur. "These models seemed to mirror the development and progression of AGS in a developing fetus," said Muotri. "It was cell death and reduction when neural development should be rising."

The cell death was trigged by the anti-viral response from the L1 molecules outside the nucleus. "We uncovered a novel and fundamental mechanism, where chronic response to L1 elements can negatively impact human neurodevelopment," said Charles Thomas, a former graduate student in the Muotri lab and first author of the study. "This mechanism seems human-specific. We don't see this in the mouse."

The researchers observed that AGS pathogenesis was similar to a retroviral infection and wondered whether existing HIV antiretroviral drugs might be effective in interfering in L1 replication. Two drugs were tested in the cell models: Stavudine and Lamivudine. Both drugs resulted in reduced L1 and cell toxicity. Cell model growth returned in all cell types and in the complex, differentiated colonies of nerve cells that comprise organoids.

The data supported the idea that HIV drugs could benefit AGS patients, Muotri said. A clinical trial led by study co-author Yanick Crow, MRCP, PhD, at Sorbonne Paris Cite University and the University of Manchester, has already started in Europe.

Muotri said the findings were illuminating and encouraging, providing a platform and impetus for further study of the pathology of neuroinflammation and drug discovery. "It's important to note that while this work focused on AGS, nerve cells in schizophrenia show an overabundance of L1 elementsand there is an overlap with other autoimmune disorders.

"This is a great example of how a fundamental basic research could be rapidly translated into clinics. Are there analogous mechanisms at work in these different diseases? Is this modeling strategy relevant for better understanding and treating them? These are questions we will now pursue."

Explore further: Researchers create model of anorexia nervosa using stem cells

More information: Charles A. Thomas et al, Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.07.009

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Visit link:
Novel stem cell-derived model created of inflammatory neurological disorder - Medical Xpress

Test results after stem cell transplant for multiple myeloma can … – Medical Xpress

August 10, 2017 Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology and Walter L. Shepeard Chair in Clinical Pathology at the Medical College of Georgia at Augusta University. Credit: Phil Jones

It's a cancer of the plasma cells, which normally make an array of antibodies that protect us from infection.

With multiple myeloma, the cells start primarily producing instead a singular product, called a monoclonal antibody, or M spike, that leaves patients vulnerable for serious infections, like pneumonia, and can even eat away at their bones.

Sophisticated laboratory tests used to both diagnose the disease then follow treatment response, can send confusing messages to patients and their physicians, particularly after stem cell therapy to try to restore a healthy antibody mix, says Dr. Gurmukh Singh. Singh, vice chair of clinical affairs for the Department of Pathology and Walter L. Shepeard Chair in Clinical Pathology at the Medical College of Georgia at Augusta University, is corresponding author of the study highlighting reasons for potential confusion in the Journal of Clinical Medicine Research.

The tests, serum protein electrophoresis and serum immunofixation electrophoresis, or SPEP/SIFE, and serum free light chain assay, or SFLCA, separate proteins into groups according to their electrical charge.

The M spike stands out as a distinctive, dense band of color among the layers of protein groups, while typical antibody levels create bands of lighter smears.

But after stem cell therapy, which first destroys cancerous plasma cells then restores healthy ones, follow up profiles often yield a lineup of antibodiescalled an oligoclonal patternthat can look eerily similar to the M spike.

The confusion comes because there again may be a prominent and likely short-lived band of proteins that emerges as the antibody mix begins, ideally, to normalize.

"We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor," Singh says.

The key clarifier appears to be the location of the malignant, monoclonal spike when the diagnosis is made compared to the location of new spikes that may show up after stem cell therapy in these oligoclonal bands, says Singh.

"If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody," Singh says, pointing toward different before and after treatment profiles on a patient.

Normally antibodies spread out in a usual sequence in these studies. "If it's in a different location, it's not the same protein," reiterates Singh. "If the location is different, this is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease," Singh says of the oligoclonal bands that can also temporarily show up in response to an infection.

He notes while the prominent bands are typically short-lived following treatment, the recognition that they are non-malignant may occur only in retrospect.

For the study, Singh and his team looked at lab and clinical data on 251 patients with multiple myeloma treated from January 2010 to December 2016; 159 of those patients received autologous stem cell transplants. Each patient had at least three tests, and at least two of the tests were following their transplant.

They found the incidence of oligoclonal patterns was significantly higher in patients who had a stem cell transplant than the patients who had chemotherapy alone: 57.9 percent compared to 8.8 percent. Only five of the 159 patients who received a transplant had an oligoclonal pattern before treatment but 92 had one afterward. More than half of the the oligoconal patterns developed within the first year following a transplant. The earliest pattern was detected at two months - as soon as the first post-transplant tests were doneand a few occurred as long as five years later.

Autologous stem cell therapy is not considered curative for most patients with multiple myeloma. There is no clear cause of the disease but the risk does increase at age 40, Singh says.

Explore further: Excessive tests don't benefit patient, do increase cost in age-related immune disorder

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more:
Test results after stem cell transplant for multiple myeloma can ... - Medical Xpress