Biopeer

Researchers discover protein linked to muscle deterioration in the elderly

Researchers at Stanford University School of Medicine found that stem cells in muscles get more garbled instructions from the body as we age, and without full instructions, the stem cells can't heal injured muscles as well. The study revealed that Wnt, a protein traditionally thought to help promote maintenance and proliferation of stem cells in many tissues, actually blocks proper communication in this instance. Researchers already know of many drugs that block Wnt signaling. "Theoretically, given the number of ways to block Wnt and Wnt signaling, one could envision this becoming a therapeutic," said Thomas Rando, associate professor of neurology at Stanford. "You could potentially enhance the healing of aged tissues by reducing this effect of Wnt signaling on the resident stem cells." Understanding how the body directs stem cells may open the door to new therapies for injuries in a host of different tissues.

Researchers at the University of Pennsylvania have demonstrated that applying physical stress can alter the structure of proteins tucked within cells, unfold them and expose new targets in the fight against disease. "We were motivated to probe molecular mechanics within cells in part by our recent findings on stem cells that show they generate their own forces, switching on and off development of different cell types," said Dennis Discher, professor of chemical and biomolecular engineering. The results of this study may increase the understanding of cellular behavior and unlock sites for drugs to interact with these proteins to treat disease.

A study led by Yi Sun at UCLA and Thomas Südhof at the University of Texas Southwestern Medical Center showed that not all embryonic stem cell lines are created equal. The scientists compared neurons generated from two NIH-approved embryonic stem cell lines and uncovered significant differences in the mature, functioning neurons from each line. "On the one hand, it may actually be good to have ES (embryonic stem) cells with a particular propensity for differentiation, because it may make it easier to get certain types of tissue," said Dr. Thomas Südhof. "On the other hand, it may also limit the ability of these ES cells to fully replicate those types of tissues."

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Stem cell transplantation increases lifespan for amyloidosis patients

Researchers at the Boston University Medical Center discovered that high-dose chemotherapy and blood stem cell transplantation can result in long-term survival for patients diagnosed with primary systemic light chain (AL) Amyloidosis, a condition where plasma cells in bone marrow produce proteins that mis-fold and deposit in tissues leading to organ failure and eventual death. The research team reviewed the records of 80 patients who received high-dose chemotherapy and blood stem cell transplantation for three years. The median survival period for these patients was about six years and 23% of them are still alive today. That's a significant improvement compared to the 2% of patients who manage to survive 10 years after traditional treatment with melphalan and prednisone. "However, efforts need to continue to be directed upon achieving a complete hematologic response in patients," said Vaishali Sanchorawala, M.D., associate professor of medicine at Boston University. "We are finding that the proportion of patients who ultimately achieve a complete response have the highest rate of long-term survival."

Scientists at the Forsyth Institute discovered a mechanism for controlling the behavior of adult stem cells. The researchers found a novel role for the proteins that are involved in cell-to-cell communication, which may help them understand the nature of the messages that control stem cell regulation. The Forsyth team used planarians (a flatworm) and other animal models to study development and regeneration. Their findings highlighted how direct cell-cell transfer of small molecules between stem cells and their neighbors can provide a blueprint for learning about regeneration. "Further analysis in both planarians and in vertebrates will provide crucial opportunities for understanding what drives stem cell behavior and may help medical science identify novel therapeutic targets," said Nestor J. Oviedo, lead author of the study.

A study published by the journal Cell Stem Cell reported that a new method for comprehensive genetic analysis can help distinguish the type of human embryo that stem cells come from. The scientists completed a thorough genome-wide analysis of the first human embryonic stem cell (or ES) line purportedly generated by Korean scientists using human eggs and somatic cell nuclear transfer, in what is sometimes referred to as cloning. That process would result in stem cells that are nearly genetically identical to a donor, and thus would be easier to use in treatment than stem cells with the genes of a new embryo. The results confirm that ntES (stem cells from "cloning") and pES (stem cells from an unfertilized egg) have distinct DNA recombination signatures. Those made from pES display a telltale genetic pattern close to the center of chromosomes. Using that knowledge, researchers showed that the Korean stem cell line was the first ever successfull pES line, meaning the first successful stem cell line using unfertilized eggs that were chemically tricked into dividing into embryos.

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Scientists aim to create soft tissue from adult stem cells

Researchers at the Columbia University Medical Center received a 2.5 million dollar grant from the National Institute of Biomedical Imaging and Bioengineering to use stem cells to engineer soft tissue. The goal is to create long-lasting soft tissue implants from mesenchymal stem cells harvested from the patient's own bone marrow or adipose tissue. "Our research has shown that mesenchymal stem cells can create tissue that is biocompatible with the host and that the continuous generation of these cells can replenish the implant to reduce shrinkage," said Jeremy Mao, associate professor of dental medicine at Columbia University Medical Center. The research team has shown that human mesenchymal stem cells can create long-lasting implants in mice. The success of this clinical trial would allow scientists to use these cells for facial and breast reconstruction.

PrimeCell Therapeutics LLC recently announced a clinical trial that assessed the safety, feasibility and efficacy of implanting autologous bone marrow stem cells into spinal cord injury (SCI) patients. Researchers treated 25 patients with SCI with autologous bone marrow stem cells at the Luis Vernaza Hospital in Guayaquil, Ecuador. After two years of treatment, 16% of the subjects could walk with crutches, 28% could walk without braces and 40% could walk on the parallels with braces. "There is evidence demonstrating significant improvement in the quality of life of patients receiving the treatment, including spinal cord regeneration and additional clinical improvements following these stem cell transplants," said Francisco Silva, vice president of research and development at PrimeCell Therapeutics.

Researchers at the Cancer Research Institute of the Slovak Academy of Sciences in Bratislava engineered mesenchymal stem cells, derived from human adipose (fat) tissue, into 'suicide genes'€™ that seek out and destroy tumors like tiny homing missiles. The scientists injected the engineered mesenchymal stem cells into mice engrafted with human colon cancer, then followed with the chemotherapy drug 5-FC. Tumor growth was inhibited by up to 68% in the animals, and they showed no toxic side effects. "œThese fat-derived stem cells could be exploited for personalized cell-based therapeutics," said Cestmir Altaner, associate professor at the Cancer Research Institute of the Slovak Academy of Sciences.

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Researchers identify key genetic themes that keep stem cells in flexible state

A team of Canadian scientists identified 1,155 genes under the control of a single gene called Oct4, the master regulator of the stem cell state. Researchers developed a comprehensive definition of stem cells on a molecular basis such that stem cells keep their DNA packed in a flexible format, keep cell division tightly controlled, prevent signals that trigger death and repair DNA. “You could call this a 'theory-of-everything' for stem cells,” said Michael Rudnicki, senior scientist at the Ottawa Health Research Institute. To conduct the study, researchers applied rigorous analysis methods using data from Stem Base, the largest stem cell gene expression database in the world. "These findings may help us to understand how the key genes which control cell fate are regulated, and how, when dysregulated, they can lead to disease," said Pearl Campbell, lead author of the study. "This may ultimately allow us to develop targeted therapies to stimulate adult stem cells within our own bodies to repair damaged tissues, and may provide further areas of exploration for the treatment of cancer."

Researchers at Children's Hospital of Boston found a new way to increase stem cell production in blood, which might pave the way for a potential treatment for leukemia patients who undergo chemotherapy or bone marrow transplants. The researchers demonstrated that a stable analog of prostaglandin is capable of enhancing the blood-forming system, both during embryonic development and after the system has been damaged. The prostaglandin, dmPGE2, was discovered after screening more than 2,500 chemicals in zebrafish. “The fact that we confirmed the zebrafish discovery in a mammalian system suggests it may also be applicable in humans,” said Wolfram Goessling, MD, PhD, of the Children's Hospital of Boston. The hospital is planning to begin a clinical trial of this drug in 2008.

Scientists at the University of Rochester are testing a new innovation in biotherapy that alters a common childhood respiratory virus, called the adenovirus, to destroy cancer cells. The researchers designed a new version of the adenovirus to selectively attack cancer cells more frequently than other cells, and it is expected to have powerful potential. "Our concept is very promising and we hope it will open the door to safer and more effective treatments," said Baek Kim, associate professor of Microbiology and Immunology at the University of Rochester Medical Center. "If this works, the most exciting part is that patients would be able to generate their own internal weapons to kill the malignant cells without having to endure a toxic element such as chemotherapy."

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Neural stem cell treatment eases Parkinson’s symptoms in primates

Researchers from Yale University, Harvard University, University of Colorado and the Burnham Institute found human neural stem cells effective in treating primates suffering from severe Parkinson’s disease. In the study, five of eight monkeys with advanced Parkinson’s disease were injected with human neural stem cells. The five monkeys had diminished tremors, were able to move and walk better, and showed better eating habits. “Not only are stem cells a potential source of replacement cells, they also seem to have a whole variety of effects that normalize other abnormalities,” said D. Eugene Redmond, professor at Yale. “The human neural stem cells implanted into the primates survived, migrated, and had a functional impact.” The results of the study are promising but it may take years to know whether similar treatment would have therapeutic value for humans with Parkinson’s symptoms.

A study, headed by Nobel Laureate Renato Dulbecco, resident at the Salk Institute for Biological Studies, demonstrated that a single cancer stem cell is sufficient to initiate and maintain a malignant tumor. The researchers found that a single cell taken from cultured LA7 cells and injected into mouse breast tissue could seed a new mammary carcinoma. “We can use single cancer stem cells to study the dynamics and behavior of cancer stem cells and their role in solid tumor formation at the single cell level,” said lead author Ileana Zucchi, molecular cancer biologist at the Institute for Biological Technology in Milan, Italy. The researchers hope that a model of a cancer stem cell system will allow them to find proteins and genes that will help in the search for human breast cancer stem cells.

A study recently published in Nature Reviews Genetics examined the feasibility of deriving human embryonic stem cell (hESC) lines without destroying living human embryos. Ronald M. Green, professor at the Dartmouth Ethics Institute, proposed six approaches – altered nuclear transfer, parthenogenesis, single-blastomere biopsy, somatic-cell dedifferentiation, the use of "dead" embryos, and the use of abnormal embryos – that would be accepted universally. “I think we can pursue hESC research and also respect the sensitivities of our fellow citizens. It's not impossible to do both,” said Green.

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More stem cell research advances

A team at the University of Melbourne’s Center for Eye Research Australia (CERA) employed, for the first time in Australia, the process of limbal stem cell transplant. Along with a team from Bernard O’Brien Institute of Microsurgery (BOBIM), they replicated the cornea using only one stem cell from the donor. The technique they used can also assist people with alkaline burns, which have damaged the surface of their eyes. Research on developing a totally bio-engineered cornea using a stem cell extracted from elsewhere on a person's body other than the eye is under progress.

Meanwhile, researchers from Harvard University and Columbia University have reported about replacement of cells, destroyed due to the paralyzing nervous system disorder, better known as Lou Gehrig's disease. The latest studies done on mice to replicate a form of ALS, show a soluble toxic compound secreting out of the disease-causing astrocytes, which researchers have not yet identified. The research is not on a conclusive phase and hence it is difficult to give a verdict on a definite cure to neurodegenerative diseases. Therefore, there is much concern about toxic detection before researchers can spell success on stem cell replacement.

Researchers at The Hospital for Sick Children (SickKids) at the University of Toronto and Harvard Medical School have found that neural stem cell development during embryogenesis may have a direct effect on abnormal brain development. Dr Freda Miller, a senior scientist in Developmental Biology in the SickKids Research Institute, and her team focused on the human genetic disorder Noonan syndrome, a disorder where the SHP-2 protein is mutated, causing abnormal development of multiple parts of the body. The team found that mutation of this protein changed the way neural stem cells generate the different cells of the embryonic brain; when SHP-2 was altered in a mouse model of Noonan syndrome, early neural development was disturbed.

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Stem cells therapies make progress

Researchers have found that stem cells can be used to reverse type 1 diabetes. They removed the immune system of 15 young diabetes patients, who had recently been diagnosed with the disorder. After this, they isolated adult stem cells from the patients’ blood and each patient was injected with his own stem cells. The results differed individually but fourteen of the patients did not need any insulin injections for the next several months. The preliminary results of the study demonstrate that this therapy may help to reduce the destruction of insulin-producing cells, which occurs in type 1 diabetes.

Meanwhile, American researchers have suggested a stem cell therapy to treat hearing loss. They have identified the ability of cochlear stem cells taken from the inner ear to develop into tissue related to the ear. They feel that this is due to the proximity of the cells to the ear and the manifestation of particular genes, which are essential for hearing. Earlier lab studies on mouse cochlear tissue prompted the researchers to conduct their study on human stem cells. The findings may help in the formulation of a therapy to repair permanent hearing loss, but further research is essential.

Another study has led researchers to believe that female stem cells are more effective than their male counterparts are. The team of scientists was studying stem cells as a possible cure for Duchene muscular dystrophy (DMD) when they made this discovery. They infused both male and female mice with stem cells from muscles and assessed the redevelopment of muscles in the mice. They found that those given stem cells from female mice showed a greater instance of muscle regeneration. This is the first time the potentiality of stem cells has been based on gender. It is extremely significant for future research.

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Stem cell therapies show potential for heart patients

For the first time, UK researchers have used stem cells to develop a heart valve. Scientists at Harefield hospital positioned bone marrow stem cells into the scaffolds formed from collagen and developed them into heart valve tissues. They hope that testing these heart valves on animals in the future will see positive results. In addition, if the procedure were put to practice on humans, there would be no need to use drugs to prevent the patient’s body from rejecting the new cells. The researchers are optimistic that in 10 years time, stem cells can be used to grow a whole heart.

Meanwhile, scientists at Rush University Medical Center found that stem cell therapy restored damaged muscle in heart patients. The researchers conducted a placebo-controlled experiment. Over a period of 2 years, they examined 53 patients who were given either a placebo or Provacel, the intravenous adult stem cell therapy, 10 days after having a heart attack. Those who were given Provacel had a 75 per cent lower chance of suffering from arrhythmic adverse events. Within six months, the overall condition of the heart and lungs of these patients had been enhanced considerably. The scientists are delighted by the positive results of these Phase 1 trials.

Another research study has examined the effects of post-menopausal age on hormone therapy for heart patients. Findings from the secondary tests of the Women’s Health Initiative (WHI) imply that women who receive hormone therapy, not more than 10 years after menopause, have lower risks of coronary heart disease (CHD), than older women do. They rechecked the data collected earlier and studied three age categories of women between 50-79. Those who had symptoms like hot flashes and night sweats were more likely to have a higher risk of CHD. However, overall the hormone therapy did not significantly prevent the risk of CHD.

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Stem cell studies make headway

An international team of researchers has revealed that the use of embryonic stem cells can check degeneration in the brain. Researchers at the Burnham Institute for Medical Research conducted a study on mice, suffering from a counterpart of Sandhoff disease. They transplanted a combination of human embryonic stem cells into the brains of the affected mice. This prevented the formation of tumors and cut down inflammation caused due to the disease. The cells replaced the damaged brain tissue and certain damaged nerve cells. The replaced nerve cells could even transmit nerve impulses showing signs that these could be fully integrated. The release of the enzyme Hex was also spurred and the mice lived 70 per cent longer. Researchers feel that giving stem cell injections can prevent the future recurrence of the disease. This multidisciplinary use of stem cells gives a new hope to sufferers of Parkinson’s, Alzheimer’s, Lou Gehrig and other such diseases too.

Meanwhile, researchers from the UT Southwestern Medical Center have discovered that a process called autophagy purges damaged embryonic stem cells. It was known that autophagy causes cell death during embryonic growth, but its exact purpose was unknown. The researchers studied mouse embryos and detected that cells without the autophagy genes, atg5 or beclin1, could not give out signals for the removal of dead cells. An increase in dead cells in the embryo could lead to growth problems, inflammation or autoimmune diseases. The researchers also found that the healthy cells in grown mice lacking the autophagy gene in their lung and retinal tissues, envelope less than 25 per cent of the dead cells, in comparison to the 75 per cent in usual cases. These findings imply that correcting the lack of autophagy can help in the treatment of such diseases.

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New discoveries in stem cell research

In a groundbreaking discovery, researchers have found a new, more ethical source of stem cells. Scientists at the Wake Forest University School of Medicine, North Carolina, USA have discovered that cells from the amniotic fluid can be used for the regeneration of damaged human organs. They took samples of amniotic fluid cells from pregnant women during routine check-ups and tested the samples on mice. The researchers came to the conclusion that the cells are ‘pluripotent’. In other words, they have the ability to grow into a range of different cells. Scientists hope that the stem cells extracted from the amniotic fluid can be adapted and later used to cure genetic disorders of the child.

On a slightly different note, research has shown that stem cells can trigger cancer in certain cases. Researchers from the University of Southern California, USA, conducted a study on 177 genes repressed by Polycomb group (PcG) proteins. They found that 77 of these genes in embryonic stem cells had traces of an enzymatic modification of DNA (known as methylation) which can be linked to cancer. The study also supports the hypothesis that epigenetic events come prior to genetic changes during the advancement of cancer. As the next step, the researchers plan to detect the reasons why some genes move from temporary to permanent repression, and aim to prevent this transition completely.

Across the globe, in Japan, doctors have developed a way to create liver cells from subcutaneous fat. As part of their study, the researchers examined samples of stem cells from the subcutaneous fat of patients. The stem cells were expected to mutate into cells that make up different organs or tissues. The researchers added growth-inducing proteins to the cells and stored them for incubation. After a period of 40 days, nearly all the cells turned into liver cells. The researchers feel that if they find a way to produce the liver cells in large numbers, they can use them for the regenerative measures that can repair damaged human livers.

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