A groundbreaking trial to test bone marrow stem cell therapy with a small group of patients with multiple sclerosis (MS) has been shown to have possible benefits for the treatment of the disease.

Bone marrow stem cells have been shown in several experimental studies to have beneficial effects in disease models of MS. The research team, led by Neil Scolding, Burden Professor of Clinical Neurosciences for the University of Bristol and North Bristol NHS Trust, have now completed a small trial in patients with MS to begin translating these findings from the laboratory to the clinic.
The procedure was well tolerated and the participants were followed up for a year. No serious adverse effects were encountered. The results of clinical scores were consistent with stable disease. The results of neurophysiological tests raised the possibility of benefit.

Professor Neil Scolding said: “We are encouraged by the results of this early study. The safety data are reassuring and the suggestion of benefit tantalising. A larger study is required to assess the effectiveness of bone marrow cellular therapy in treating MS. We are hopeful that recruitment to this phase 2/3 study may begin towards the end of this year.

“Research into the underlying mechanisms is ongoing and vital, in order to build on these results. We believe that stem cells mobilised from the marrow to the blood are responsible, and that they help improve disease in several ways, including neuroprotection and immune modulation.”

The aim of the trial was to find out what effects, good or bad, bone marrow stem cells has on patients with MS, and their disability.

Bone marrow is known to contain stem cells capable of replacing cells in many types of tissues and organs – and so is of great interest to those working to develop new treatments for many diseases, including those affecting the nervous system.

Immune cells use a bungee-like nanotube to snare dangerous cells, according to new research funded by the Medical Research Council (MRC).

The findings by researchers from Imperial College London show that natural killer (NK) cells use this bungee, called a membrane nanotube, to destroy cells that could otherwise escape them.

NK cells are the first line of defence against dangerous cells, such as tumour cells and cells infected with bacteria and viruses, and researchers are keen to understand how they help the body fight infection and stop tumours from growing. Ultimately, it may be possible to design drugs that harness the NK cells’ ability to fight disease.

Prior to this study, scientists understood that NK cells can kill their target cells by attaching onto them, forming a connection called an immune synapse, which they use to pass toxic molecules into the target cell. However, sometimes the target cells move away from the NK cells to escape being destroyed.

The researchers took video footage of the cells using the bungee-like tube to keep hold of their target cells. The NK cells either pulled the target cells back into direct contact to be killed, or killed them from a distance.

Dr Kevin Moreton, Board Programme Manager for Infections and Immunity at the Medical Research Council said: “Understanding how the human immune system protects the body is critical to developing new treatments for a range of conditions from infectious diseases, autoimmune diseases, through to allergies. The MRC funded this study as part of our core strategy and ongoing commitment to researching the body’s natural protection and defence mechanisms.”

Professor Daniel Davis, corresponding author of the study at Imperial College London said: “Natural Killer cells are cells that are really good at killing tumours and virus-infected cells. It was thought they kill these diseased cells only by sticking to them tightly for several minutes. These new movies show that in fact they also tether cells with long membrane connections and can pull diseased cells back into contact. We think they may also use these nanotubes to kill them from a distance.

“The movies show the process vividly but the next step is difficult because we have to know where and when these processes are important in your body, and the technology to see such thin nanotubes in the body hasn’t been invented yet! It’s a very new research area and we need to learn how the process works precisely so that we can then think about ways to design drugs that help immune cells kill,” added Professor Davis.

When a target cell moves away from an NK cell, it normally moves ‘head’ first, at around eight micrometres per minute. Today’s research shows that when the NK cell pulls its target cell back using the nanotube bungee, it moves much faster, at around fourteen micrometres per minute. The study also showed that membrane nanotubes dramatically increase an NK cell’s chance of killing its target cell from a distance. The next step will be to find out exactly how the bungee tubes help immune cells kill their target cells.

University of Michigan scientists have identified a new reservoir for hidden HIV-infected cells that can serve as a factory for new infections. The findings, which appear online March 7 in Nature Medicine, indicate a new target for curing the disease so those infected with the virus may someday no longer rely on AIDS drugs for a lifetime.

“Antiviral drugs have been effective at keeping the virus at bay. However once the drug therapy is stopped, the virus comes back,” says senior author of the study Kathleen L. Collins, M.D., Ph.D., associate professor of both internal medicine and microbiology and immunology at the U-M Medical School.

In people infected with HIV (human immunodeficiency virus), the virus that causes AIDS, there’s an unsolved problem with current anti-viral drugs. Though life-saving, they cannot root the virus out of the body. Infected cells are able to live on, undetected by the immune system, and provide the machinery for the virus to reproduce and spread.

Important new research by U-M has discovered that bone marrow, previously thought to be resistant to the virus, can contain latent forms of the infection.

“This finding is important because it helps explain why it’s hard to cure the disease,” Collins says. “Ultimately to cure this disease, we’re going to have to develop specific strategies aimed at targeting these latently infected cells.”

“Currently people have to take anti-viral drugs for their entire life to control the infection,” she says. “It would be easier to treat this disease in countries that don’t have the same resources as we do with a course of therapy for a few months, or even years. But based on what we know now people have to stay on drugs for their entire life.”

Using tissue samples, U-M researchers detected HIV genomes in bone marrow isolated from people effectively treated with antiviral drugs for more than six months.

While further studies are needed to demonstrate that stem cells can harbor the HIV virus, the study results confirm that HIV targets some long-lived progenitor cells, young cells that have not fully developed but mature into cells with special immune functions. When active infection occurs the toxic effects of the virus kill the cell even as the newly made viral particles spread the infection to new target cells.

“Our finding that HIV infects these cells has clear ramifications for HIV disease because some of these cells may be long-lived and could carry latent HIV for extended periods of time,” she says. “These HIV cell reservoirs can be induced to generate new infections.”

The new research gives a broader view of how HIV overwhelms the body’s immune system and devastates its ability to regenerate itself.

Globally more than 30 million people are infected with HIV, including millions of children. Improvements have been made since the 1990s in the way the disease is treated that has led to an 85 percent to 90 percent reduction in mortality.

“Drugs now available are effective at treating the virus, making HIV more of a chronic disease than a death sentence,” Collins says. “This has made a huge impact in quality of life, however only 40 percent of people worldwide are receiving anti-viral drugs and unfortunately that means that not everybody is benefiting.”

Tumor budding at the invasive tumor front of colorectal cancer is recognized as an independent prognostic factor significantly related to both lymph node and distant metastasis. Several lines of evidence seem to suggest that tumor buds may, to some extent, represent malignant colorectal cancer stem cells because of their potential for migration and re-differentiation locally and at sites of metastasis. However, phenotypic characterization of cancer stem cells in general is still debated although at least 8 putative stem cell markers have been suggested including CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. Little is known about the potential of these proteins to act as prognostic biomarkers in patients with colorectal cancer and most of these proteins have never before been explored within tumor buds themselves.

A research article published in the World Journal of Gastroenterology addressed this problem. Considering the apparent stem cell-like properties of tumor buds and association of budding with adverse clinical outcomes, the research team led by Dr. Alessandro Lugli performed immunohistochemical staining of 8 putative cancer stem cell markers, namely CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. The expression within tumor buds was evaluated, their frequency of occurrence and their potential prognostic significance in patients with colorectal cancer were determined.

Their findings showed that expression of EpCAM and particularly of ABCG5 within the tumor buds of colorectal cancer are frequent events. Moreover, expression of EpCAM or ABCG5 within tumor buds themselves has the potential to stratify patients with colorectal cancer into prognostic subgroups. This was particularly pronounced for patients with node-negative disease.

The results of this study could have important implications for patients with lymph node-negative colorectal cancer. Stratification of this group of patients could help to identify those likely to have a particularly poor outcome who could perhaps be considered for adjuvant therapy.

The study is characterized technically by an excellent application of immunohistochemistry and provides interesting evidence to aid the understanding of the correlation between cancer stem cell markers at the invasive front of colorectal cancer and prognosis. The findings suggest that EpCAM and ABCG5 in tumor buds may be useful biomarkers of poor outcome in this subgroup of patients. However, further studies are necessary to address the important issue of whether EpCAM- or ABCG5-positive tumor buds indeed represent migrating colorectal cancer stem cells.

A heart patient’s own skin cells soon could be used to repair damaged cardiac tissue thanks to pioneering stem cell research of the University of Houston’s newest biomedical scientist, Robert Schwartz.

His new technique for reprogramming human skin cells puts him at the forefront of a revolution in medicine that could one day lead to treatments for Alzheimer’s, diabetes, muscular dystrophy and many other diseases.

Schwartz brings his ground-breaking research to UH as the Cullen Distinguished Professor of Biology and Biochemistry and head of UH’s new Center for Gene Regulation and Molecular Therapeutics. He also is affiliated with the Texas Heart Institute at St. Luke’s Episcopal Hospital in the Texas Medical Center, where he is director of stem cell engineering.

“Professor Schwartz’s work will save lives, and his decision to pursue this pioneering research at UH is a big leap forward on our way to Tier-One status,” said John Bear, dean of the UH College of Natural Sciences and Mathematics. “Together with the many other outstanding scientists we’ve assembled here, Schwartz will help make this university a major player in medical research.”

Schwartz devised a method for turning ordinary human skin cells into heart cells. The cells developed are similar to embryonic stem cells and ultimately can be made into early-stage heart cells derived from a patient’s own skin. These then could be implanted and grown into fully developed beating heart cells, reversing the damage caused by previous heart attacks. These new cells would replace the damaged cardiac tissue that weakens the heart’s ability to pump, develops into scar tissue and causes arrhythmias. Early clinical trials using these reprogrammed cells on actual heart patients could begin within one or two years.

Although Schwartz is not the first scientist to turn adult cells into such stem cells, his improved method could pave the way for breakthroughs in other diseases. Schwartz’s method requires fewer steps and yields more stem cells. Armed with an effective way to make induced stem cells from a patient’s own skin, scientists can then begin the work of growing all kinds of human cells.

For example, new brain cells could treat Alzheimer’s patients or those with severe brain trauma, or a diabetic could get new insulin-producing cells in the pancreas. Generating new kidney, lung or liver tissue is also possible, with scientists even being able to one day grow an entirely new heart or other organ from these reprogrammed cells. Additionally, Schwartz and his team are working on turning induced stem cells into skeletal muscle cells to treat muscular dystrophy.

“We’re trying to advance science in ways folks never even dreamed about,” Schwartz said. “The idea of having your own bag of stem cells that you can carry through life and use for tissue regeneration is at the very cutting edge of science.”

This latest biomedical hire is a major step in the UH Health Initiative, an effort aimed at having the university become a world-class center for medical research. Creating new cross-disciplinary academic and health-related research opportunities for faculty and students is crucial to this initiative, as are collaborations with other Texas Medical Center member institutions. One of its top goals is to increase the amount of sponsored research expenditures awarded to UH, which is a key factor in attaining Tier-One status.

“Dr. Schwartz will expand UH’s expertise in promising new areas of scientific discovery to alleviate human disease. By recruiting premier scientists like Schwartz, UH is fast becoming a major player in the regional biomedical research community,” said Kathryn Peek, assistant vice president of University Health Initiatives at UH.

Stem cell research in multiple sclerosis (MS) has been given a much-needed shot in the arm thanks to a partnership between the UK’s largest charity supporting people affected by the condition and the UK’s only charity dedicated to supporting stem cell research.

The MS Society and the UK Stem Cell Foundation (UKSCF) today (Thursday) formally marked the beginning of the collaboration by announcing a call for research grant applications that can now dip into a dedicated pot of joint-funding up to £1million.

Dr Doug Brown, Biomedical Research Manager at the MS Society, said the partnership would “pump prime” and speed up stem cell research.

He added: “We’re delighted to announce this partnership that is the first of its kind and look forward to receiving applications for research funding.

“Stem cells are showing real promise in MS, and the sooner we can take the science from the bench to the bedside, the sooner people with MS will get the answers they so desperately need.”

The potential of stem cells as a treatment for MS has long been the subject of much interest and debate.

In 2009, the MS Society convened an International Consensus Meeting for stem cell therapies and MS and a number of international experts put forward the view that MS is a condition that could benefit greatly from targeted and increased stem cell research investment and the collaboration is in direct response to that.

The UK is a recognised global leader in all aspects of stem cell research and in an ideal position to advance stem cell techniques into the clinic for the benefit of billions of people around the globe.

Progress in this area is being hindered, however, by a critical gap between currently available government and private funding and the countless promising research projects in need of financial assistance.

Without increasing commitment and funding for research and a push for clinical trials, there are fears these benefits will not be realised.

“People with MS and the world’s leading researchers have made it clear that more research is needed now,” Dr Brown added.

New research from scientists at Queen Mary, University of London shows how the most common type of children’s brain cancer can arise from stem cells.

Scientists know relatively little about medulloblastomas or why some cases respond better to treatments than others.

The new research, published today in Oncogene*, shows that medulloblastomas can grow from a type of brain stem cell and that these cancers are a distinct form of the disease which may require a completely different approach to treatment.

Medulloblastomas account for one in five of all children’s brain tumours. They are most common in children between the ages of three and eight but they can also affect young adults.

Silvia Marino, Professor of Neuropathology at Queen Mary, University of London, led the study. She said: “This type of brain tumour can pose a great challenge to doctors. In some children, treatment works well but in others the cancer is aggressive and far harder to treat.

“As scientists we’ve been trying to understand how these cancers which look the same can behave so differently.

“This study is a major advance for us because it shows for the first time that some of these tumours develop from endogenous stem cells.

“This is important for two reasons. First, it could help us to tell which cancers will respond well to treatment and which will need a more aggressive therapy. Second, this new understanding could help us to find much-needed new drugs for the disease.”

Previous research has shown that human brains contain a small number of stem cells – called neural stem cells – which enable the brain to repair itself to some degree. Professor Marino and her team studied equivalent cells taken from mouse brains.

They found that two particular genes called Rb and p53, which are already known to play a role in cancer, could malfunction in these cells and allow the cells to grow uncontrollably. They also found that in mice, these cells turned into medulloblastomas.

The researchers then looked more closely at the genetic makeup of these tumours and found a particular pattern which they compared with tumours taken from patients with medulloblastomas. They found that patients whose tumours also had this genetic pattern were those with the worst survival chances.

The researchers believe that their findings are a crucial first step in understanding the most aggressive form of this disease. They can now begin to look for new ways to tackle the disease in a more effective and possibly less toxic way.

In a developing animal, stem cells proliferate and differentiate to form the organs needed for life. A new study shows how a crucial step in this process happens and how a reversal of that step contributes to cancer.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, shows for the first time that three proteins, called E2f1, E2f2 and E2f3, play a key role in the transition stem cells make to their final, differentiated, state.

These proteins help stimulate stem cells to grow and proliferate. But once stem cells begin to differentiate into their final cell type – a cell in the retina or in the lining of the intestine, for example – the same three proteins switch function and stop them from dividing any more.

The research also shows how these proteins can switch course yet again in cells that have mutations in the retinoblastoma (Rb) gene. Mutated Rb genes occur in many types of cancer, suggesting that these E2f proteins might offer a safe and novel therapeutic target in these tumors.

The findings are published in back-to-back papers in the Dec. 17 issue of the journal Nature

“We show that these E2fs are gene activators in stem cells but then switch to gene repressors when stem cells begin differentiating,” says Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at Ohio State’s James Cancer Hospital and Solove Research Institute. Leone headed the first of the two Nature studies and is a co-author on the second.

“This is a very important step in the process of differentiation,” Leone says. “As organs form during development, there comes a time when their growth must stop because an organ needs only a certain number of cells and no more. The switch by these proteins from activators to repressors is essential for that to happen. “Before this, there was no suspicion that these regulatory proteins had any role in differentiated cells,” says Leone. “It was thought they were important only in proliferating cells like stem cells. But that’s not true.”

Leone and his colleagues show the function of the proteins in differentiation in mouse embryos, retinas, lenses and intestines.

They also show how the three proteins could revert back to gene activators in cancer cells and promote tumor growth in cancers with Rb mutations. “In this case, these proteins are acting abnormally relative to the surrounding tissue, so they might provide a safe therapeutic target,” Leone explains. “If we can inactivate these E2fs in cancer cells, perhaps we can prevent further tumor growth without having a major affect on healthy cells.”

The mouse is a standard laboratory model organism, but there are currently few resources that describe conventional techniques to analyze blood and blood-forming tissues in this species. A newly released set of compact and easy-to-use laboratory resources from Cold Spring Harbor Laboratory Press fills this gap. Mouse Hematology features step-by-step protocols for the preparation, enumeration, and microscopic examination of peripheral blood, bone marrow, and other hematopoietic tissues in the mouse. The laboratory manual is accompanied by a DVD with video demonstrations of the techniques and a poster of blood cell types for easy identification at the microscope.

Mouse Hematology was written by James J. Lee (Mayo Clinic Arizona) and two members of his lab, Michael P. McGarry and Cheryl A. Protheroe. All three have extensive experience employing hematological procedures in mice, and they wrote the book partly in response to numerous requests for help in preparing samples and identifying blood cell types. “Our goal here is to present standards and procedures for the examination of blood and blood-forming tissues of the laboratory mouse,” the authors write in the preface of the book. “The described methodologies will allow for the morphological examination of blood, bone marrow, and/or hematopoietic tissues in research protocols and, in turn, will provide a greater understanding of mouse models of human disease.”

The manual describes how to collect blood samples from adult mice and mouse pups; determine hematocrit and use a hemocytometer to count cells; and smear, fix, and stain blood films. Detailed protocols for performing bone marrow biopsies and for preparing bone marrow smears and suspensions for cytospin analysis are also provided. High-quality video demonstrations of most of the techniques are included on the DVD.

In addition to protocols, Mouse Hematology contains full-color images and detailed descriptions of the morphology of mature blood cells and their progenitors. The poster also presents examples of different blood cell types and will be a useful reference at the microscope.

This set of resources will be useful to laboratory scientists at all levels who work with mice to study hematopoiesis, stem cells, the immune system, and genetic diseases that affect the blood.

A groundbreaking discovery two years ago that turned ordinary skin cells back into an embryonic or “pluripotent” state was hailed as the solution to the controversial ethical question that has plagued stem-cell science for the past decade.

But is it the solution? Or have iPS cells (induced pluripotent stem cells) simply added a new dimension to the legal, social and ethical debates that are an important and necessary part of stem-cell advances.

This was the central question discussed by an international group of leading scientists, bioethicists and legal scholars who attended a workshop organized by the Stem Cell Network this summer in Barcelona. Outcomes of the workshop will be published Dec. 10 in the journal Cell. Among the issues summarized in the article are consent, privacy, clinical translation and intellectual property rights for iPS cells that are derived for scientific study and/or clinical therapies.

Timothy Caulfield, research director at the University of Alberta’s Health Law Institute and principal investigator at the Stem Cell Network, says that while iPS technology eliminates some of the ethical issues specific to embryonic stem-cell research it also adds new challenges.

“From a legal perspective, iPS technology is fascinating and complex. For example, if an iPS cell can be made into a functional human gamete, the potential exists for reproductive purposes. What would this mean for donor consent, concerns about cloning and rights of a potential child to know its parents,” said Caulfield.

“What could this mean to assisted reproduction practices and would-be parents with no other option? If anything, we know considerable thought and policy development needs to be placed around these and other issues.”

Michael Rudnicki, scientific director of the Stem Cell Network, agrees and says the promise of stem cell advances using iPS cells is staggering. “If iPS cells can be made safe for clinical therapies, it will ultimately make the delivery faster and more economical. But as a scientist I am cautious. So much is based on future prospects and there is much work that needs to be done in the labs before it becomes a therapeutic reality,” says Rudnicki.