Natural therapy: Cells

Showing posts with label Cells. Show all posts

Tuesday, August 6, 2013

Scientists: Sleeping Stem Cells Could Hold Key to Treatment of Aggressive Blood Cancer

by Rukmani Krishna on? August 02, 2013 at 12:02 AM Cancer News Rather than displacing healthy stem cells in the bone marrow as previously believed, the cancer is putting them to sleep to prevent them forming new blood cells, discovers scientists studying an aggressive form of leukaemia. Scientists: Sleeping Stem Cells Could Hold Key to Treatment of Aggressive Blood Cancer
The finding offers the potential that these stem cells could somehow be turned back on, offering a new form of treatment for the condition, called Acute Myeloid Leukaemia (AML). The work was led by scientists at Queen Mary, University of London with the support of Cancer Research UK's London Research Institute.

Around 2,500* people are diagnosed with AML in the UK each year, both young and old. Although AML is curable in some the majority die from this disease.

Normally, the bone marrow produces haematopoietic stem cells which mature into "adult" blood cells. In people with AML the bone marrow is invaded by leukaemic myeloid cells which aren't able to develop into normal functioning blood cells.

The result is that the body does not have enough red blood cells or platelet cells, which can cause symptoms of anaemia, such as tiredness, and increase the risk of excessive bleeding. Patients are also more vulnerable to infection as the white blood cells, which fight bacteria and viruses, are not properly formed.

Dr David Taussig, from the Barts Cancer Institute at Queen Mary, University of London, who led the research, said: "The widely accepted explanation has held that AML causes bone marrow failure by depleting the bone marrow of normal haematopoietic stem cells by killing or displacing them.

"However, we have found that samples of bone marrow in both mice models and patients with AML contain the same, or more, of these normal stem cells than usual. So the cancer isn't getting rid of them, instead it appears to be turning them off so they aren't going on to form healthy blood cells.

"If we can find out how the cancer cells are doing this, we can look at exploiting it to find ways to wake these stem cells up. This is very important as, while the cure rate for younger patients can be around 40 per cent, in older patients it is much lower. The treatments we have, such as chemotherapy and bone marrow transplants, just aren't very successful in this older patient group."

The scientists studied the levels of haematopoietic stem cells (HSC) in the bone marrow of mice transplanted with human AML. They found the numbers of normal mouse HSCs stayed the same, however what did change was that the HSCs were no longer going through the stages of development which finally results in the formation of new blood cells.

The findings were confirmed by the analysis of bone marrow from 16 patients with AML.

Professor Peter Johnson, Cancer Research UK's chief clinician, said: "Although major progress has been made in treating AML over the years, there's still an urgent need for more effective treatments to improve long-term survival. This study takes us an important step forwards in our understanding of what's going on in the bone marrow of people with AML, an area that we have not known enough about previously, and the challenge now is to turn this understanding into new treatments for patients."

Dr Taussig added: "Usually when the body is stressed, the stem cells become very active. For example, if you have a haemorrhage, they will jump into action to produce more new blood cells. The cancer cells are somehow over-riding this and our next phase of work will concentrate on how they are doing this."

Source-Eurekalert

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Monday, August 5, 2013

Scientists: Sleeping Stem Cells Could Hold Key to Treatment of Aggressive Blood Cancer

Around 2,500* people are diagnosed with AML in the UK each year, both young and old. Although AML is curable in some the majority die from this disease.

The findings were confirmed by the analysis of bone marrow from 16 patients with AML.

Source-Eurekalert

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Wednesday, July 24, 2013

Researchers Find Way to Multiply Insulin-Producing Cells

Efforts to make this treatment possible have been limited by a dearth of insulin-producing beta cells that can be removed from donors after death, and by the stubborn refusal of human beta cells to proliferate in the laboratory after harvesting.

The new technique uses a cell conditioning solution originally developed to trigger reproduction of cells from the lining of the intestine.

"Until now, there didn't seem to be a way to reliably make the limited supply of human beta cells proliferate in the laboratory and remain functional. We have not only found a technique to make the cells willing to multiply, we've done it in a way that preserves their ability to make insulin," said Michael McDaniel, PhD, professor of pathology and immunology.

Lead author Haytham Aly, PhD, a postdoctoral research scholar, reported on his work with beta cells and was approached by Thaddeus Stappenbeck, MD, PhD, associate professor of pathology and immunology, who studies autoimmune problems in the gut.

Stappenbeck had developed a medium that causes cells from the intestine's lining to proliferate in test tubes.

The ability to produce large quantities of human beta cells in the laboratory gives the researchers hope that they could one day be transplanted into patients with type 1 diabetes.

If the new availability of laboratory-grown beta cells makes it possible to treat patients with transplants from one donor instead of multiple donors, Stappenbeck noted, that might reduce the risk of immune system rejection of the transplants.

The findings are now available online in PLOS ONE.

Source-ANI

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Friday, July 19, 2013

'Human Liver' from Stem Cells Created

by Sheela Philomena on? July 04, 2013 at 11:43 AM Genetics & Stem Cells News Scientists have created human liver tissue from stem cells. Creating lab-grown tissue to replenish organs damaged by accident or disease is a Holy Grail for the pioneering field of research into the premature cells known as stem cells. 'Human Liver' from Stem Cells Created
Now Takanori Takebe of the Yokohama City University Graduate School of Medicine and a team report in the journal Nature that they grew tissue "resembling the (human) adult liver" in a lab mouse.

They first created induced pluripotent stem (iPS) cells which they mixed with other cell types and coaxed into "liver buds" -- the precursor clusters that develop into a liver.

The buds, each about five millimetres (0.2 inches) big, were then transplanted onto a mouse brain, where they were observed transforming into a "functional human liver" complete with blood vessels, the scientists wrote.

"To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells," said the report.

The technique has yet to be tested in humans, but serves as an important proof of concept, it added.

Stem cells are infant cells that can develop into any part of the body.

Until a few years ago, when iPS cells were created, the only way to obtain stem cells was to harvest them from human embryos.

This is controversial because it requires the destruction of the embryo, a process to which religious conservatives and others object.

iPS cells are easily-obtainable mature cells that are "reprogrammed" into a versatile, primitive state from where they can develop into any kind of cell in the body.

Takebe told a press conference ahead of the report's release that the man-made liver was observed through a replacement glass skull that was fitted around the mouse's brain.

The liver developed blood vessels which fused with those of the animal.

It also performed certain human-specific liver functions -- producing proteins and processing specific drugs.

"We have concluded that this liver is functioning," the scientist said. "We think this is enough for improving the survival after liver failure."

Scientists commenting on the research described it as promising.

"This science opens up the distinct possibility of being able to create mini-livers from the skin cells of a patient dying of liver failure," said Malcolm Alison, professor of stem cell biology at the Queen Mary University of London.

"Human mature liver cells transplanted on their own can fail to thrive, but if immature liver cells are first combined with their normally nurturing supportive cells, they can mature in the transplanted host and function efficiently," he said in a statement issued by the Science Media Centre.

Dusko Ilic from Kings College London said "the promise of an off-shelf-liver seems much closer than one could hope even a year ago", but the strategy has yet to be proven in humans.

"Whilst the title of the paper is 'functional human liver', these liver buds do not contain the biliary structures (which drain toxins out of the liver) or immune cells that characterise real human liver," added Stuart Forbes, professor of transplantation and regenerative medicine at the University of Edinburgh.

Chris Mason of University College London said the buds may be useful for drug testing in the lab, which is currently restricted by the limited availability of liver cells from human cadavers.

Takebe said the method may also work in organs like the pancreas, kidneys or lungs, but it would be another 10 years before trials are done in humans.

One key requirement would be to shrink the "buds" to a much smaller size so they can be injected into the bloodstream and taken up by the body internally, he said.

Source-AFP

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Wednesday, July 17, 2013

Gene That Controls Aggressiveness in Breast Cancer Cells Discovered

The researchers, whose findings are published this week in the journal Cell, report that the ZEB1 gene is held in a poised state in basal non-CSCs, such that it can readily respond to environmental cues that consequently drive those non-CSCs into the dangerous CSC state. Basal-type breast carcinoma is a highly aggressive form of breast cancer. According to a 2011 epidemiological study, the 5-year survival rate for patients with basal breast cancer is 76%, compared with a roughly 90% 5-year survival rate among patients with other forms of breast cancer.

"We may have found a root source, maybe the root source, of what ultimately determines the destiny of breast cancer cells-their future benign or aggressive clinical behavior," says Whitehead Founding Member Robert Weinberg, who is also a professor of biology at MIT and Director of the MIT/Ludwig Center for Molecular Oncology.

Transcription factors are genes that control the expression of other genes, and therefore have a significant impact on cell activities. In the case of ZEB1, it has an important role in the so-called epithelial-to-mesenchymal transition (EMT), during which epithelial cells acquire the traits of mesenchymal cells. Unlike the tightly-packed epithelial cells that stick to one another, mesenchymal cells are loose and free to move around a tissue. Previous work in the Weinberg lab showed that adult cancer cells passing through an EMT are able to self-renew and to seed new tumors with high efficiency, hallmark traits of CSCs.

Other earlier work led by Christine Chaffer, a postdoctoral researcher in the Weinberg lab, demonstrated that cancer cells are able to spontaneously become CSCs. Now Chaffer and Nemanja Marjanovic have pinpointed ZEB1, a key player in the EMT, as a gene critical for this conversion in breast cancer cells.

Breast cancers are categorized into at least five different subgroups based on their molecular profiles. More broadly these groups can be subdivided into the less aggressive ‘luminal'' subgroup or more aggressive ‘basal'' subgroup. The aggressive basal-type breast cancers often metastasize, seeding new tumors in distant parts of the body. Patients with basal breast cancer generally have a poorer prognosis than those with the less aggressive luminal-type breast cancer.

Chaffer and Marjanovic, a former research assistant in the Weinberg lab, studied non-CSCs from luminal- and basal-type cancers and determined that cells from basal cancers are able to switch relatively easily into CSC state, unlike luminal breast cancer cells, which tend to remain in the non-CSC state.

The scientists determined that the difference in ZEB1''s effects is due to the way the gene is marked in the two types of cancers. In luminal breast cancer cells, the ZEB1 gene is occupied with modifications that shut it down. But in basal breast cancer cells, ZEB1''s state is more tenuous, with repressing and activating markers coexisting on the gene. When these cells are exposed to certain signals, including those from TGFs, the repressive marks are removed and ZEB1 is expressed, thereby converting the basal non-CSCs into CSCs.

So what does this new insight mean for treating basal breast cancer?

"Well, we know that these basal breast cancer cells are very plastic and we need to incorporate that kind of thinking into treatment regimes," says Chaffer. "As well as targeting cancer stem cells, we also need to think about how we can prevent the non-cancer stem cells from continually replenishing the pool of cancer stem cells. For example, adjuvant therapies that inhibit this type of cell plasticity may be a very effective way to keep metastasis at bay."

Marjnaovic agrees but cautions that the model may not be applicable for every cancer.

"This is an example of how adaptable cancer cells can be,," says Marjanovic, who is currently a research assistant at the Broad Institute. "We have yet to determine if ZEB1 plays a similar role in all cancer types, but the idea that cancer cells reside in a poised state that enables them to adapt to changing environments may be a mechanism used by many cancers to increase their aggressiveness."

This work is supported Vertex Scholars Program, the National Science Foundation (NSF), Jerome and Florence Brill Fellowship, Croucher and Ludwig Research Fellowship, the National Institutes of Health (NIH) (1 F32 GM099153-01A1, HD 045022 and R37CA084198).

Source-Newswise

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Wednesday, July 10, 2013

Research Finds Too Many 'Healing' Cells Delays Wound Healing

"Improvement of lymphedema is important for treatment of skin ulcers," said Makoto Sugaya, M.D., Ph.D., a researcher involved in the work from the Department of Dermatology at the University of Tokyo in Tokyo, Japan. "It is not just fluid retention, but inflammatory cells and cytokines that cause delayed wound healing."

To make this discovery, scientists used two groups of mice. The first group showed severe lymphatic dysfunction. The second group was normal. Researchers administered skin wounds and found that the mice with lymphatic dysfunction showed delayed would healing as compared to the normal mice. Analysis showed that the delayed would healing in the lymphedematous skin is the result of too many mast cells and elevated IL-10 expression, both of which can now be therapeutic targets for future drug development.

"Wound healing is something most people take for granted until there's a problem," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "However, wound healing is a complex process involving immune as well as non-immune cells and problems that arise can be very serious, even if it started as a minor wound. This report provides an immunological explanation for why some wound healing is delayed, and it ultimately may help set a course for therapies that accelerate wound healing."

Source-Eurekalert

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Monday, July 8, 2013

Vitamin C's Influence on Stem Cells Key to Normal Development in Mice

The study led by UC San Francisco researchers found that vitamin C assists enzymes that play a crucial role in releasing the brakes that keep certain genes from becoming activated in the embryo soon after fertilization, when egg and sperm fuse.

The discovery might eventually lead to the use of vitamin C to improve results of in vitro fertilization, in which early embryos now are typically grown without the vitamin, and also to treat cancer, in which tumor cells abnormally engage or release these brakes on gene activation, the researchers said.

In the near term, stem-cell scientists may begin incorporating vitamin C more systematically into their procedures for growing the most healthy and useful stem cells, according to UCSF stem-cell scientist Miguel Ramalho-Santos, PhD, who led the study.

In fact, the unanticipated discovery emerged from an effort to compare different formulations of the growth medium, a kind of nutrient broth used to grow mouse embryonic stem cells in the lab.

Rather than building on any previous body of scientific work, the identification of the link between vitamin C and the activation of genes that should be turned on in early development was serendipitous, Ramalho-Santos said.

Working in Ramalho-Santos' lab, graduate student Kathryn Blaschke and postdoctoral fellow Kevin Ebata, PhD, were comparing different commercial growth media for mouse stem cells. The researchers began exploring how certain ingredients altered gene activity within the stem cells. Eventually they discovered that adding vitamin C led to increased activity of key enzymes that release the brakes that can prevent activation of an array of genes.

The brakes on gene activation that vitamin C helps release are molecules called methyl groups. These methyl groups are added to DNA at specific points along the genome to prevent specific genes from getting turned on.

During the development of multicellular organisms, humans among them, different patterns of methylation arise in different cells as methyl groups are biochemically attached to DNA at specific points along the genome during successive cell divisions. Normally this gradual methylation, a key part of the developmental program, is not reversible.

But after fertilization and during early development, a class of enzymes called "Tet" acts on a wide array of the methyl groups on the DNA to remove these brakes, so that genes can be activated as needed.

The UCSF researchers demonstrated that Tet enzymes require vitamin C for optimal activity as they act to remove the methyl groups from the DNA and to stimulate gene activity that more faithfully mimics in cultured stem cells what occurs at early stages of development in the mouse embryo.

"Potential roles for vitamin C in the clinic - including in embryo culture media used during in vitro fertilization, which currently do not contain vitamin C, and in cancers driven by aberrant DNA methylation - deserve exploration," Ramalho-Santos, said.

The study is published in the journal Nature.

Source-ANI

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