Human blood stem cells engineered to kill HIV

A proof-of-principle study has demonstrated that it is possible to engineer human blood stem cells into cells that can target and kill HIV-infected cells. The result is the equivalent of a genetic vaccine which is not only good news in the fight against HIV - the process could also be used against a range of chronic viral diseases.

In the study researchers from the UCLA AIDS Institute and colleagues took the “killer” T cells that help fight infection, known as CD8 cytotoxic T lymphocytes, from an HIV-infected individual. The researchers then identified the molecule known as the T-cell receptor – the molecule that guides the T cell in recognizing and killing HIV-infected cells. Although these cells are able to destroy HIV-infected cells, they do not exist in enough quantities to clear the virus from the body. So the researchers cloned the receptor and genetically engineered human blood stem cells, then placed the stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also found that HIV-specific T-cell receptors have to be matched to an individual in much the same way that an organ is matched to a transplant patient.
The next step is to test this strategy in a more advanced model to determine if it would work in the human body, said co-author Jerome A. Zack, UCLA professor of medicine in the division of hematology and oncology and associate director of the UCLA AIDS Institute. And with the results of the study suggesting the strategy could be an effective weapon in the fight against AIDS, the researchers also hope to expand the range of viruses against which this approach could be used.

"We have demonstrated in this proof-of-principle study that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells," said lead investigator Scott G. Kitchen, assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute. "These studies lay the foundation for further therapeutic development that involves restoring damaged or defective immune responses toward a variety of viruses that cause chronic disease, or even different types of tumors."

Love as pain relief ....

As science continues to unravel the mysteries of ourselves and the world around us at a furious pace, it can sometimes feel like the boffins are proving things that many of us feel we already know or take for granted. This interesting example comes from the Stanford University School of Medicine, where scientists have found that intense feelings of love are as effective at relieving pain as painkillers or even illicit drugs.
The last few decades have shown us that pain is not simply a symptom of trauma, but is a discreet disease entity in its own right that can affect the entire nervous system. Advances in neuro-imaging have allowed scientists a better look at the areas in which pain is processed, how the brain is affected and how it changes our thoughts and emotions, in an effort to create a multi-disciplinary treatment for pain.

Neuroimaging was able to link the activation of reward systems in the brain with the feelings of euphoria and contentment that are often distinguished by the early stages of a relationship. With Functional Magnetic Resonance Imaging (fMRI) they found that the area of the brain that processes pain and the area of the brain that is involved in reward-processing are situated close together. Close neurological ties between the two areas meant activation of the reward-processing area could affect the pain-processing area.

Stanford study
Fifteen lovesick individuals were tested in the first nine months of their relationship. They were subjected to moderate and high thermal pain, and shown pictures of their partner, pictures of another attractive and familiar friend, and underwent a word-association task designed to be distracting. Both the partner pictures and distraction technique reported a significant reduction in pain, or analgesia, and only the partner pictures activated the brain's reward-processing areas; the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex.

The study suggests that neural activation of the reward-processing areas via non-pharmacological means could be a powerful action on the pain experience, and could help future work with pain management in humans.
"When people are in this passionate, all-consuming phase of love, there are significant alterations in their mood that are impacting their experience of pain," said Sean Mackey, MD, PhD, chief of the Division of Pain Management, associate professor of anesthesia and senior author of the study. "We're beginning to tease apart some of these reward systems in the brain and how they influence pain. These are very deep, old systems in our brain that involve dopamine — a primary neurotransmitter that influences mood, reward and motivation."

Other studies running concurrently are using brain imaging to train patients to control the experience of pain; to identify the changes in the brain experienced during chronic pain that amplify the pain experience, and how to reverse them; to examine distraction techniques as a viable method of pain management; to study pain-processing via the spinal cord; the use of neurotoxins as a novel method of pain management; the use of intravenous lidocaine as an effective pain relief; the pain experience and contributing factors; and sensitization to pain following repeated use of opiates.
The study was published online in PLoS ONE.

Ancient body clock discovered that helps to keep all living things on time

A group of Cambridge scientists have successfully identified the mechanism that drives our internal 24-hour clock, or circadian rhythm. It occurs not only in human cells, but has also been found in other life forms such as algae, and has been dated back millions of years. Whilst the research promises a better understanding of the problems associated with shift-work and jet-lag, this mechanism has also been proven to be responsible for sleep patterns, seasonal shifts and even the migration of butterflies.

The study from the Institute of Metabolic Science at the University of Cambridge discovered that red blood cells contain this 24-hour rhythm. In the past, scientists assumed this rhythm came from DNA and gene activity but unlike most cells, red blood cells do not contain DNA.
During this study, the Cambridge scientists incubated healthy red blood cells in the dark at body temperature for several days, sampling them at regular intervals. It was discovered that the levels of peroxiredoxins (proteins that are produced in blood), underwent a 24-hour cycle. Virtually all known organisms contain peroxiredoxins.
"The implications of this for health are manifold," said Akhilesh Reddy, lead author of the study. "We already know that disrupted clocks – for example, caused by shift-work and jet-lag – are associated with metabolic disorders such as diabetes, mental health problems and even cancer. By furthering our knowledge of how the 24-hour clock in cells works, we hope that the links to these disorders – and others – will be made clearer. This will, in the longer term, lead to new therapies that we couldn't even have thought about a couple of years ago."

A second study by scientists working together at the Universities of Edinburgh and Cambridge, and the Observatoire Oceanologique in Banyuls, France, identified a similar 24-hour rhythm in marine algae. Once again, the scientists held a previous belief that the circadian clock was driven by gene activity, but both the algae and the red blood cells proved this theory wrong.
"This groundbreaking research shows that body clocks are ancient mechanisms that have stayed with us through a billion years of evolution," said Andrew Millar of the University of Edinburgh's School of Biological Sciences. "They must be far more important and sophisticated than we previously realized. More work is needed to determine how and why these clocks developed in people – and most likely all other living things on Earth – and what role they play in controlling our bodies."

Cell reprogramming breakthrough could mend broken hearts

Heart disease remains one the biggest killers in the Western world. When a heart attack or heart failure occurs, permanent damage often affects the heart, destroying live cells and leaving the patient with irreversible scarring. This scarring can often lead to a terminal condition or increase the risk of danger of future heart attacks. Now scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have discovered a new technique to create healthy beating heart cells from structural cells. These advancements mean that in the future doctors could be able to repair damaged hearts.

Our human heart comprises of cardiomyocytes (beating heart cells) and cardiac fibroblasts, which provide a support structure and secrete signals. In research published in the current issue of the Journal Cell, scientists were able to successfully reprogram fibroblasts within the heart to transform them into cardiomyocytes.

"Scientists have tried for 20 years to convert nonmuscle cells into heart muscle, but it turns out we just needed the right combination of genes at the right dose," said lead researcher Dr. Masaki Ieda.
With this success of these trials the researchers have discovered evidence which would suggest that independent adult cells within the body can be reprogrammed from one cell type to another whilst by-passing the stem cell state. This discovery could have repercussions in all areas of medicine. Whilst direct cellular reprogramming may erase the issues involving the use of stem cells, it could also remove the risk that some stem cells may later develop into tumors.

The first stage of the cellular reprogramming occurs over three days, before the cells start to adopt the characteristics of cardiac muscle. However it may take up to seven weeks before the cells are fully reprogrammed into healthy beating heart cells.
"The ability to reprogram fibroblasts into cardiomyocytes has many therapeutic implications," said GICD director Dr. Deepak Srivastava. "Half of the cells in the heart are fibroblasts, so the ability to call upon this reservoir of cells already in the organ to become beating heart cells has tremendous promise for cardiac regeneration. Introducing the defined factors, or factors that mimic their effect, directly into the heart to create new heart muscle would avoid the need to inject stem cells into the heart and all the obstacles that go along with such cell-based therapies."

While direct cellular reprogramming hopes to offer many advantages, further laboratory work will need to be carried out before this technique can be used easily and effectively within our hospital systems.
"Direct reprogramming has not yet been done in human cells," Dr. Srivastava added. "And, the hope is still to find small molecules, rather than genetic factors, that can be used to direct the cell-fate switch."