Stem Cell Clinic

Stem Cell Therapy Selectively Targets and Kills Cancerous Tissue – Anti Aging News

1538 1 Posted on Aug 11, 2017, 6 a.m.

Researchers have created a method to kill cancerous tissue without causing the harmful side effects of chemotherapy.

Medical researchers at the University of California, Irvine have created a stem cell-based method to zero in on cancerous tissue. This method kills the cancerous tissue without causing the nasty side effects of chemotherapy. Such side effects are avoided by treating the disease in a more localized manner. The advancement was spearheaded by associate professor of pharmaceutical sciences Weian Zhao. The details of the stem cell therapy were recently published in Science Translational Medicine.

About the new Stem Cell Therapy

Zhao's team programmed stem cells derived from human bone marrow to pinpoint the specific properties of cancerous tissue. They implemented a portion of code to these engineered cells to identify stiff cancerous tissue, lock onto it and implement therapeutics. The researchers safely used this new stem cell therapy in mice to kill metastatic breast cancer that had moved to the lungs. They transplanted these engineered stem cells in order for the teamto pinpoint and settle in the site of the tumor.

Once the stem cells reached the tumor, they released enzymes referred to as cytosine deaminase. The mice were then provided with an inactive chemotherapy known as prodrug 5-flurocytosine. The tumor enzymes stimulated the chemotherapy into action. Zhao stated his team zeroed in on metastatic cancer that occurs when the disease moves to additional parts of the body. Metastatic tumors are especially dangerous. They are responsible for90 percent of all cancer deaths.

Why the new Stem Cell Therapy is Important

Zhao is adamant his stem cell therapy represents an important newparadigm in the context of cancer therapy. Indeed, Zhao has blazed a trail in a new direction that others will likely follow in the years to come. It is possible his new stem cell therapy serves as an alternative and more effective means of treating cancer. This stem cell therapy will serve as an alternative to numerous forms of chemotherapy that typically have nasty side effects. Chemotherapy certainly kills plenty of growing cancer cells yet it can also harm healthy cells. The new type of treatment keys in on metastatic tissue that allows for the avoidance of the undesirable side effects produced by chemotherapy.

Though the published piece describing this stem cell therapy is centered on breast cancer metastases within thelungs, the method will soon be applicable to additional metastases. This is due to the fact that numerous solid tumors are stiffer than regular tissue. The new system does not force scientists to invest time and effort to pinpoint and create a brand new protein or genetic marker for each kind of cancer.

The Next Step

At this point in time, Zhao's team has performed pre-clinical animal studies to show the treatment is effective and safe. They plan to segue to human studies in the coming months and years. Zhao's team is currently expanding to additional types of cells such as cancer tissue-sensing and engineered immune system CAR-T (T cells) to treat metastasizing colon and breast cancers. Their goal is totransform this technology for the treatment of additional diseases ranging from diabetes to fibrosis and beyond.

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Stem Cell Therapy Selectively Targets and Kills Cancerous Tissue - Anti Aging News

Mutation-directed CAR T cell therapy feasible in recurrent glioblastoma – medwireNews

medwireNews: Treatment with autologous chimeric antigen receptor (CAR) T cells directed against the epidermal growth factor receptor variant III (EGFRvIII) mutation is feasible and well tolerated in patients with recurrent glioblastoma, indicates a first-in-human study.

But barriers to the clinical efficacy of the therapy exist, says the research team, including the inhibitory tumor microenvironment, which becomes even more immunosuppressive after CAR T cells.

Lead author Marcela Maus (Massachusetts General Hospital, Boston, USA) and colleagues chose the EGFRvIII mutation as it is a tumor-specific, oncogenic, and immunogenic epitope expressed in around 30% of newly diagnosed cases of glioblastoma.

In this phase I study, reported in Science Translational Medicine, 10 patients with EGFRvIII-expressing glioblastoma that had progressed after at least one prior line of therapy were given a single infusion of an autologous EGFRvIII-directed CAR T product within a week of progression.

There were no dose-limiting toxicities, and no evidence of off-target EGFR-directed effects such as rash, diarrhea, or pulmonary symptoms or systemic cytokine release syndrome.

Neurologic events were observed in three patients and included a seizure at day 9 in one patient and neurologic decline in two patients, at day 15 in one case and postoperatively in the other. Although such events are common in glioblastoma patients due to the nature of the disease, Maus et al say that they could also result from CAR T-induced immune responses in the confined intracranial space.

They were unable to formally assess efficacy as the majority (n=7) of study participants underwent surgery following infusion of the CAR T cells. But one patient was alive and required no further treatment for 18months or more after the infusion. A further two patients were also alive at the time of analysis, but they showed signs of disease progression by imaging criteria.

The surgical intervention allowed the researchers to evaluate not only tissue-specific trafficking of CAR T cells and on-target effects, but also the tumor microenvironment in situ.

Analysis of tumor samples showed the presence of EGFRvIIICAR T cells in the brain, with higher levels in the four patients who had surgery within 14days of the infusion than in the three who underwent surgery at later timepoints.

And comparison of post-infusion samples with matched samples obtained before the infusion revealed a significant decline in the expression levels of EGFRvIII in five of the seven participants with available samples. Such a decrease in antigen expression in the remaining tumor bed and tissue is indicative of on-target effects, say Maus and colleagues.

But they also found that the expression of several immunosuppressive molecules, including indoleamine 2,3-dioxygenase 1, was markedly increased in post- versus pre-infusion samples, and noted elevations in the relative proportion of immunosuppressive FoxP3+ regulatory T cells after infusion.

These findings suggest that CART-EGFRvIII activation induced a compensatory multifactorial immunosuppressive response in situ, say the investigators, adding that it could potentially be overcome with existing drugs that target immunosuppressive molecules.

Study author Donald ORourke, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, USA, told the press: This is an early stage trial, but we are encouraged by the fact that the cells got into the brain, proliferated, and reduced the level of antigen with very little toxicity to the patients. We can build on this as a therapeutic option for these patients. It gives us clues on what to do next.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. 2017 Springer Healthcare part of the Springer Nature group

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Mutation-directed CAR T cell therapy feasible in recurrent glioblastoma - medwireNews

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

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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.

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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.

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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

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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!

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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.

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