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The use of bone stem cells combined with a degradable rigid material that inserts into broken bones and encourages real bone to re-grow has been developed at the Universities of Edinburgh and Southampton.

Researchers have developed the material with a honeycomb scaffold structure that allows blood to flow through it, enabling stem cells from the patient’s bone marrow to attach to the material and grow new bone. Over time, the plastic slowly degrades as the implant is replaced by newly grown bone.  Scientists developed the material by blending three types of plastics. They used a pioneering technique to blend and test hundreds of combinations of plastics, to identify a blend that was robust, lightweight, and able to support bone stem cells. Successful results have been shown in the lab and in animal testing with the focus now moving towards human clinical evaluation.

“Fractures and bone loss due to trauma or disease are a significant clinical and socioeconomic problem.  This collaboration between chemistry and medicine has identified unique candidate materials that support human bone stem cell growth and allow bone formation. The collaborative strategy offers significant therapeutic implications.  We were able to make and look at a hundreds of candidate materials and rapidly whittle these down to one which is strong enough to replace bone and is also a suitable surface upon which to grow new bone.” said Professor Mark Bradley, of the University of Edinburgh’s School of Chemistry

“We are confident that this material could soon be helping to improve the quality of life for patients with severe bone injuries, and will help maintain the health of an aging population.”

The study, published in the journal Advanced Functional Materials .

Sources:

Scientists Are Rebuilding Hearts With Stem Cells

Every two minutes someone in the UK has a heart attack.

Every six minutes, someone dies from heart failure.

During an attack, the heart remodels itself and dilates around the site of the injury to try to compensate, but these repairs are rarely effective. If the attack does not kill you, heart failure later frequently will.  “No matter what other clinical interventions are available, heart transplantation is the only genuine cure for this,” says Paul Riley, professor of regenerative medicine at Oxford University. “The problem is there is a dearth of heart donors.”  Transplants have their own problems – successful operations require patients to remain on toxic, immune-suppressing drugs for life and their subsequent life expectancies are not usually longer than 20 years.  The solution, emerging from the laboratories of several groups of scientists around the world, is to work out how to rebuild damaged hearts. Their weapons of choice are reprogrammed stem cells.

These researchers have rejected the more traditional path of cell therapy that you may have read about over the past decade of hope around stem cells – the idea that stem cells could be used to create batches of functioning tissue (heart or brain or whatever else) for transplant into the damaged part of the body.  Instead, these scientists are trying to understand what the chemical and genetic switches are that turn something into a heart cell or muscle cell. Using that information, they hope to program cells at will, and help the body make repairs.

It is an exciting time for a technology that no one thought possible a few years ago. In 2007, Shinya Yamanaka showed it was possible to turn adult skin cells into embryonic-like stem cells, called induced pluripotent stem cells (), using just a few chemical factors.

His technique radically advanced stem cell biology, sweeping aside years of blockages due to the ethical objections about using stem cells from embryos. He won the Nobel prize in physiology or medicine for his work in October. Researchers have taken this a step further – directly turning one mature cell type to another without going through a stem cell phase.

At Oxford, Riley has spent almost a year setting up a lab to work out how to get heart muscle to repair itself. The idea is to expand the scope of the work that got Riley into the headlines last year after a high-profile paper published in the journal Nature in which he showed a means of repairing cells damaged during a heart attack in mice. That work involved in effect turning the clock back in a layer of cells on the outside of the heart, called the epicardium, making adult cells think they were embryos again and thereby restarting their ability to repair.

During the development of the embryo, the epicardium turns into the many types of cells seen in the heart and surrounding blood vessels. After the baby is born this layer of cells loses its ability to transform. By infusing the epicardium with the protein thymosin β4 (Tβ4), Riley’s team found the once-dormant layer of cells was able to produce new, functioning heart cells. Overall, the treatment led to a 25% improvement in the mouse heart’s ability to pump blood after a month compared with mice that had not received the treatment.

Riley says finding ways to replace damaged cells via transplantation, the dominant research idea for more than a decade, has faltered. Scientists have tried out a variety of adult stem cells – derived from areas such as bone marrow, muscle and fat – turned them into heart cells and transplanted them into animal models, which initially showed good results.  But those results could never be repeated in humans with the same degree of success. “In humans, moving into clinical trials, the actual benefit, from a meta-analysis just on bone-marrow-derived cells, is a meagre 3% improvement,” he says. “That’s barely detectable clinically and unfortunately isn’t going to make a vast amount of difference to your overall quality of life.”  The original impression from rodent studies was that the transplanted cells would become new muscle and contribute to improving damaged areas, but Riley says that idea has fallen out of favour. “All they do, if anything at all, is to secrete factors that will help the heart sustain the injury, rather than necessarily offer long-term regeneration.”

That is where the reprogrammers get going. Find the chemical factors that will make a cell (a skin cell, say, or a piece of scar tissue) think it is in the womb, so it switches certain genes on and others off and becomes a new heart cell, and you can avoid the large-scale transplant altogether. All you need is an infusion of the right drugs and resident cells will do all the required repair work.

The process requires an understanding of how an embryo develops and what cues nature uses to grow all the body’s cell types from just a sperm and an egg. This ability to regenerate does not quite stop at birth: injure a one-day-old mouse’s heart, for example, and it will completely regenerate. Injure it again after a week and the heart will scar. “Within seven days, it goes from completely repairable to the adult wound-healing default position,” says Riley. “We want to understand what happens during that window.”

Many scientists believe the secrets of how to regenerate tissue are linked with an understanding of how to reverse the ageing process. Saul Villeda, of the University of California, presented work at the recent annual meeting of the Society for Neuroscience in where he showed that blood from young mice reversed some of the effects of ageing in older mice, improving learning and memory to a level comparable with much younger animals. Older mice had an increased number of stem cells in their brains and there was a 20% increase in connections between brain cells.

Though his work is yet to be published in a peer-reviewed journal, Villeda speculated the young blood was likely to be working in the older mice by increasing levels of chemical factors that tend to decline as animals get older. Bring these back, he says, and “all of a sudden you have all of these plasticity and learning and memory-related genes that are coming back”.

Prof Deepak Srivastava has already transformed scar-forming cardiac cells in mice into beating heart cells, inside living animals, using a set of chemical factors. His results were published last April in Nature.  “We’ve redeployed nature’s own toolkit in these cells to convert non-muscle cells that are in the heart into new muscle. More than half of the cells in the heart are not muscle [but] architectural cells called fibroblasts that are meant to support the muscle,” he says.

“We had the idea that if we could somehow fool those cells into thinking that they should become muscle, then we have a vast reservoir of cells that already exist within the organ that might be able to be called upon to regenerate the heart from within.”

He injected three chemical factors – called Gata4, Mef2c and Tbx5, collectively known as GMT – into the damaged region of a heart and, within a month, the non-beating cells that normally ended up becoming scar tissue had become functioning heart cells that had integrated with their neighbors.  “The factors get taken up by the fibroblasts and the non-muscle population of cells and they initiate a genome-wide switch of the program of the cells so that it now begins to activate thousands of muscle-specific genes and it turns off thousands of fibroblast genes.”

Srivastava’s direct reprogramming technique takes Yamanaka’s work further because it allows scientists to turn one type of cell into another without having to go through a stem cell phase in between, thus reducing the risk that any future therapy might induce cancer.  The method has been proven to work, so far only in Petri dishes, for blood, liver and brain cells. “Ultimately, as we learn enough about each cell type, it’s likely we might be able to make most cell types in the body with this direct reprogramming approach,” he says.

The tough task for all these scientists – from those working specifically on the heart such as Riley to those working more generally on all cell types such as Srivastava – is to identify and catalogue the thousands of chemical factors that are at work in the various stages of cell development, and that are the keys to the transformation of one cell into another.

“We’re trying to do the same experiments we did in the heart in the pig’s heart because it is very similar in size and physiology to human hearts. If it works there and it is safe, then we’d be ready for a human clinical trial,” says Srivastava.

Epidermal growth factor has been found to speed the recovery of blood-making stem cells after exposure to radiation, according to Duke Medicine researchers. The finding could open new options for treating cancer patients and victims of dirty bombs or nuclear disasters.

Reported in the Feb. 3, 2013, issue of the journal Nature Medicine, the researchers explored what had first appeared to be an anomaly among certain genetically modified mice with an abundance of epidermal growth factor in their bone marrow. The mice were protected from radiation damage, and the researchers questioned how this occurred.

“Epidermal growth factor was not known to stimulate hematopoiesis, which is the formation of blood components derived from hematopoietic stem cells,” said senior author John Chute, M.D., a professor of medicine and professor of pharmacology and cancer biology at Duke University. “However, our studies demonstrate that the epidermal growth promotes hematopoietic stem cell growth and regeneration after injury.”  Hematopoietic stem cells, which constantly churn out new blood and immune cells, are highly sensitive to radiation damage. Protecting these cells or improving their regeneration after injury could  benefit patients who are undergoing bone marrow transplantation, plus others who suffer radiation injury from accidental environmental exposures such as the Japanese nuclear disaster in 2011.”

The Duke researchers launched their investigation using mice specially bred with deletions of two genes that regulate the death of endothelial cells, which line the inner surface of blood vessels and are thought to regulate the fate of hematopoietic stem cells. Blood vessels and the hematopoietic system in these mice were less damaged when exposed to high doses of radiation, improving their survival.  An analysis of secretions from bone marrow endothelial cells of the protected mice showed that epidermal growth factor (EGF) was significantly elevated up to 18-fold higher than what was found in the serum of control mice.  The researchers then tested whether EGF could directly spur the growth of stem cells in irradiated bone marrow cultured in the lab. It did, with significant recovery of stem cells capable of repopulating transplanted mice.  Next, the Duke team tried the approach in mice using three different solutions of cells in animals undergoing bone marrow transplants. One group received regular bone marrow cells; a second group got bone marrow cells from donors that had been irradiated and treated with EGF; a third group got bone marrow cells from irradiated donors treated with saline.  The regular bone marrow cells proliferated well and had the highest rate of engraftment in the recipient mice. But mice that were transplanted with the cells from irradiated/EGF-treated donors had 20-fold higher engraftment rate than the third group.

Additional studies showed that EGF improved survival from a lethal radiation exposure, with 93 percent of mice surviving the radiation dose if they subsequently received treatment with EGF, compared to 53 percent surviving after treatment with a saline solution.

Chute said it appears that EGF works by repressing a protein called PUMA that normally triggers stem cell death following radiation exposure.

“We are just beginning to understand the mechanisms through which EGF promotes stem cell regeneration after radiation injury,” Chute said. “This study suggests that EGF might have potential to accelerate the recovery of the blood system in patients treated with chemotherapy or radiation.”

Source:  Duke Health.org

The collaborative work of medical scientists and physicians across the globe has resulted in a major medical milestone: the world’s 1 millionth blood stem cell transplant, a procedure that has become a proven and essential therapy for many patients battling blood cancers like leukemia and lymphoma, as well as other critical diseases.

The Worldwide Network for Blood and Marrow Transplantation (WBMT) announced the landmark achievement today. The WBMTa nonprofit scientific organization whose mission is promoting excellence in stem cell transplantation, stem cell donation and cellular therapysaid the 1 millionth transplant occurred in late December 2012. The finding is based on data collected by WBMT international member organizations involved in blood stem cell transplantation, which were analyzed and verified by the WBMT.

“One million transplants is a milestone that may surprise many people, because blood stem cell transplants were viewed as a rare procedure until the last decade or so,” said Dietger Niederwieser, M.D., president of the WBMT and professor of medicine in the division of hematology and medical oncology at the University Hospital of Leipzig, Germany. “But important discoveriesand the vital cooperation of many scientists and physicians around the worldhave dramatically improved outcomes for patients who undergo stem cell transplantation.”

The first blood stem cell transplant was reported by Dr. E. Donnall Thomas in 1957, who received the Nobel Prize in 1990 for pioneering the use of this innovative approach to treatment of leukemia and other life-threatening diseases.

By the late 1960s, as knowledge of the requirements for matching patients with donors evolved, physicians were performing successful allogeneic transplants, using blood-forming stem cells from sibling donors (among the first in U.S., Holland and France). In 1973, the first successful transplant between two unrelated people occurred in New York, when a young boy received a transplant from a donor identified as a match through a blood bank in Denmark. In 1988, the first successful umbilical cord blood transplant was performed in Paris.

Since then, a near-exponential rise in all types of blood stem cell transplants, particularly from unrelated donors, has occurred. This is largely thanks to the willingness of now more than 20 million voluntary stem cell donors worldwide. Today, unrelated transplants are often as successful as those that use family donors.

International partners will help make this continued growth possible. Already, data from the World Marrow Donor Association (WMDA), a WBMT partner, show that nearly half of the transplants performed with unrelated donors cross an international border. International donor registries not only expand the pool of potential donors, they help advance the global science of transplantation through the exchange of information.

“It must be especially emphasized that WBMT has contributed to the advances of blood stem cell transplants in emerging countries in the Asia-Pacific region and in the other areas of the world, where the awareness to this medical procedure is sharply increasing,” said Yoshihisa Kodera, vice president of WBMT, chairman of APBMT and professor of Aichi Medical University, Japan.

The World Health Organization (WHO) has recognized transplantation as an important global task, recently recognizing the WBMT as a non-governmental organization (NGO). “Transplantation has extended the lifespan of hundreds of thousands of patients worldwide and enhanced their quality of life,” said Luc Noël, M.D., of WHO. “It has become the standard of care for many patients, and should no longer be restricted to affluent countries or individuals.”

Today, more than 70 malignant and non-malignant diseases are treated routinely with blood stem cell transplantation, providing new cures for patients around the globe. The procedure technique itself has improved considerably because of dedicated cancer centers but also because of collaboration and cooperation among scientists, clinicians, nurses and data managers, as well as the 19 international scientific societies that establish standards, collect data on the procedure and analyze outcomes. In patients with optimal conditions, disease-free survival rates are now reaching more than 90 percent.

“Worldwide, more than 50,000 patients a year are receiving transplants, in regions ranging from the Asia-Pacific to the Mid-East to Central America,” said Dennis Confer, M.D., treasurer of the WBMT and chief medical officer of the U.S.-based National Marrow Donor Program^® (NMDP). “The curative potential of this therapy will only increase, thanks to the commitment and collaboration of researchers and physicians across the globe.”

BERN, Switzerland, Jan. 30, 2013 (GLOBE NEWSWIRE) – ( www.globenewswire.com )