Treating cancer as a chronic disease

March 30, 2012 By Kevin Hattori in Cancer

Professor Karl Skorecki

New research from the Technion-Israel Institute of Technology Rappaport Faculty of Medicine and Research Institute and the Rambam Medical Center may lead to the development of new methods for controlling the growth of cancer, and perhaps lead to treatments that will transform cancer from a lethal disease to a chronic, manageable one, similar to AIDS.

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By placing cancer cells in and near a growth developed from a population of human stem cells, scientists have demonstrated that the cancer cells grow and proliferate more robustly when exposed to human cells than they do in a typical petri dish or mouse model. The cancer cell population is also more diverse than had previously been understood.  The research was published in the current advanced online issue of the journal Stem Cells. Maty Tzukerman, Rambam senior research scientist and the project leader and senior co-author on the report, says that this model will facilitate targeted drug discovery aimed at blocking the cancer cell self-renewal process.

Previous studies have determined that some tumor cells appear to be differentiated, while others retain the self-renewal property that makes cancer so deadly. According to Technion Professor Karl Skorecki, director of Medical Research and Development at Rambam Health Care Campus and senior co-author on the report, this new research attempts to understand how cancer grows, and to find ways to halt the runaway replication.

In order to mimic the human cancer environment as closely as possible, the research team developed a teratoma - a tumor made of a heterogenous mix of cells and tissues - by enabling the differentiation of human embryonic stem cells into a variety of normally occuring human cell lines on a carrier mouse. The human cellular teratoma constitutes a new platform of healthy human cells for monitoring the behavior and proliferation of human cancer cells.

For this study, the team took cells from one woman's ovarian clear cell carcinoma and injected them either into or alongside the human stem cell-derived environment. "We noticed very early on, rather strikingly, that the human cancer cells grow more robustly when they are in the teratoma environment compared to any other means in which we grew them, such as in a mouse muscle or under the skin of a mouse," says Skorecki.

Harvesting stem cells from milk tooth could save your child’s life

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Mar 30, 2012 at 1:07 PM

Tags: Dental research, Dental stem cells, Milk tooth, Stem cell research, Stem cells

Is your child about to lose her milk tooth? Instead of throwing it away, you can now opt to use it to harvest stem cells in a dental stem cell bank for future use in the face of serious ailments. Now that’s a tooth fairy story coming to life. Still relatively new in India, dental stem cell banking is fast gaining popularity as a more viable option over umbilical cord blood banking. Stem cell therapy involves a kind of intervention strategy in which healthy, new cells are introduced into a damaged tissue to treat a disease or an injury.

“The umbilical cord is a good source for blood-related cells, or hemaotopoietic cells, which can be used for blood-related diseases, like leukaemia (blood cancer). Having said that, blood-related disorders constitute only four percent of all diseases,” Shailesh Gadre, founder and managing director of the company Stemade Biotech, told IANS. ”For the rest of the 96 percent tissue-related diseases, the tooth is a good source of mesenchymal (tissue-related) stem cells. These cells have potential application in all other tissues of the body, for instance, the brain, in case of diseases like Alzheimer’s and Parkinson’s; the eye (corneal reconstruction), liver (cirrhosis), pancreas (diabetes), bone (fractures, reconstruction), skin and the like,” he said.

Mesenchymal cells can also be used to regenerate cardiac cells. Dental stem cell banking also has an advantage when it comes to the process of obtaining stem cells. ”Obtaining stem cells from the tooth is a non-invasive procedure that requires no surgery, with little or no pain. A child, in the age group of 5-12, is any way going to lose his milk tooth. So when it’s a little shaky, it can be collected with hardly any discomfort,” Savita Menon, a pedodontist, said. ”Moreover, in a number of cases, when an adolescent needs braces, the doctor recommends that his pre-molars be removed. These can also be used as a source for stem cells. And over and above that, an adult’s wisdom tooth can also be used for the same purpose,” Gadre added.

Therefore, unlike umbilical cord blood banking which gives one just one chance – during birth – the window of opportunity in dental stem cell banking is much bigger. ”Of course, age is still a big factor,” added Menon. “A child’s milk tooth has more potency than a wisdom tooth. The ability of a young one’s cells to multiply is twice as higher as anyone else. “Pankaj Kala is one of those who opted for dental stem cell banking for his child. ”I lost my mother to cardiac arrest when she was just 45. She was also a diabetic. After that I decided that I will do everything possible to protect my family from harm. I missed the opportunity of umbilical cord blood banking in the case of my daughter when she was born; so when she was six, we went for dental stem cell banking,” Kala, who is in the jewellery business in Mumbai, told IANS.

“It’s been two years now and I have decided to go for the procedure for the second child too. Even my wife will go for stem cell banking using her wisdom tooth. In my case, however, it will be difficult since I had gone for root canal treatment in my wisdom tooth and therefore it’s not healthy,” he added. Anish Jain, another parent who has got his son’s milk tooth extracted for stem cell banking, said: “I know stem cell therapy is a relatively new field, but I didn’t want to have regrets later about not doing anything that could help my child if he suffers from any ailment. “As of now, dental stem cell banking in India is offered by a select few companies, like Stemade and Store Your Cells. The procedure and then preservation of the stem cells can cost around Rs.100,000 for a period of 21 years.

“Around 20 percent of those who have come to us for dental stem cell banking are doctors,” said Gadre, who added they collect 60-70 samples every month. There are however sceptics. ”Research is still on in stem cell therapy; so to tell people that harvesting your stem cells can save you from any serious disease is still a premature statement,” said a doctor.

Basketball’s influence on stem cell treatments in sports medicine

As the basketball frenzy that accompanies March Madness draws to the fever pitch of the Final Four, it brings to mind that basketball is a high contact sport. A quick peek at the NBA injured list reveals a catalog of breaks and tears affecting tendons, ligaments and bones.

The pressure to improve performance and search for quick recoveries has led some celebrity athletes to seek out stem cell treatments overseas and in the U.S. Among NBA players to get stem cell treatments are Jason Kidd, Tracy McGrady, Amar Stoudemire, Allan Houston and Kenyon Martin,according to a Sports Illustrated article.

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They underwent microfracture surgery to extract mesenchymal stem cells from bone barrow to repair damaged tissue. Although the practice of high profile athletes seeking this treatment has grabbed a lot of headlines, it’s not the kind of publicity that helps stem cell medicine in the country says Dr. Jason Dragoo, a Stanford University School of Medicine orthopedic surgery and sports medicine professor.

Dragoo said in a phone interview that the publicity has actually had a negative impact on the development of clinically proven stem cell therapies for orthopedic medicine and how it is perceived.”Because of this market pressure, private clinics have been offering stem cells treatments both here in the USA as well as around the world. Often these treatments have not been studied and are not regulated in any way. FDA regulations have also severely limited new clinical trials in stem cell therapy in the USA.”

The ethical debate of using embryonic stem cells taken from fetuses has been sidestepped to some extent by the viability of adult stem cells for stem cell therapy. Although the U.S. Food and Drug Administration permits cells being extracted from individuals, transformed into stem cells and re-inserted back into the same person, it requires that the conversion involve no more than water, preservatives and storage products. Anything more than that, the FDA policy goes, would be classified as a drug therapy and need to go through the proper application protocol.

But a much-awaited decision by the U.S. District Court in Washington, DC expected in May that may resolve a four-year old battle between the FDA and Regenerative Science in Colorado could represent a sea change in how autologous adult stem cell treatments are regulated. The FDA is seeking to prevent the company from providing autologous adult stem cell treatment for musculoskeletal and spinal injuries. If the FDA were to lose, anyone with a medical license could develop autologous stem cells and inject them back into patients, without any regulatory oversight, according to a Cell Press article.

Although stem cells there are the focus of numerous clinical trials, they are mainly for cancer and rare diseases, with most being conducted outside the United States. While there have been some developments for sports medicine applications produced by research from academic institutions, there have been no clinical trials for stem cell treatments in sports medicine in the United States because of the U.S. Food and Drug Administration’s reservations about using adult stem cells. Despite the laxer regulations in Japan, China and Europe, it’s not in the financial interest of companies there to spend the money to do clinical trials if they don’t have to.

Among the most interesting applications for orthopedic medicine are the restoration of articular cartilageand patching defects in joint cartilage, with the hope of resurfacing arthritic joints in the future, Dragoo said. Stanford is preparing to initiate its own clinical trial next year looking at inducible stem cells.

“This technique takes adult cells and make them young again by inserting four genes which makes the cells immature and allows them to be directed into different types of tissues,” Dragoo said.

“There are a lot more trials for the use of stem cells for diseases that are fatal or nearly fatal because there are no good answers,” Dragoo said. “That’s totally different than a young healthy athlete who is trying to improve their performance or recover from an injury. It’s a very different feeling than someone battling a disease like cancer and the FDA has encouraged clinical trials to develop compassionate use of stem cells. Orthopedic medicine is a much lower priority.”

HEART PATIENTS AND STEM CELLS

HOUSTON -

Doctors from the Texas Heart Institute at St. Luke's Episcopal Hospital have found that patients with heart failure may be able to repair the damaged areas of the heart with stem cells from the patient's own bone marrow.

Doctors presented the findings at the American College of Cardiology’s 61st Annual Scientific Session Saturday.

The results are from a multi-center clinical study that measured the possible benefits of using a patient’s own bone marrow cells to repair damaged areas of the heart suffering from severe heart failure, a condition that affects millions of Americans.

The expectation is that the study will pave the way for potential new treatment options and will be important to designing and evaluating future clinical trials.The study, which was the largest such investigation to date, found that the hearts of the patients receiving bone marrow derived stem cells showed a small but significant increase in the ability to pump oxygenated blood from the left ventricle, the heart’s main pumping chamber, to the body.

“This is exactly the kind of information we need to move forward with the clinical use of stem cell therapy,” said Emerson Perin, MD, PhD, Director of Clinical Research for Cardiovascular Medicine at THI, and one of the study’s lead investigators.

“The bone-marrow derived stem cells are helpful to the injured heart when they are themselves biologically active,” added Dr. James T. Willerson, the study’s principal investigator and President and Medical Director of THI.

“This study moves us one step closer to being able to help patients with severe heart failure who have no other alternatives.”

The study was conducted by the Cardiovascular Cell Therapy Research Network, the national consortium to conduct such research funded by the National Institutes of Health’s National Heart, Lung, and Blood Institute.

The study involving 92 patients was conducted at five sites, including THI, between 2009 and 2011.

Researchers found that left ventricular ejection fraction increased by a small but significant amount (2.7%) in patients who received stem cell therapy.

The study also revealed that the improvement in ejection fraction correlated with the number of certain stem cells known as CD34+ and CD133+ in the bone marrow.

Patients’ bone marrow cells were also sent to biorepository, where studies were done on the phenotypes and functional characteristics of the cells.

Younger patients had a higher content of CD34+ and CD133+ cells in their bone marrow and had higher ejection fractions after stem cell treatment.

This kind of analysis is essential for autologous (using a patient’s own cells) therapy, said Dr. Perin.

They will help identify which patients will most likely benefit from cell therapy.

Such information is also important in designing future trials.

South Africa: Local Scientists in Stem Cell Breakthrough

22 MARCH 2012

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A group of scientists from South Africa's Council for Scientific and Industrial Research (CSIR) have established a groundbreaking biomedical stem cell technology - a first for Africa - which could hold the key to finding cures for some of the contintent's biggest diseases.

The CSIR announced on Tuesday that its gene expression and biophysics group had generated the first induced pluripotent stem cells (iPSCs) in Africa.

"The ability to grow these stem cells, a complex skill currently available at only a handful of institutions in the US, Europe and Japan, has revolutionised the way that researchers are able to investigate and understand diseases," the CSIR said in a statement.

"It also holds enormous promise in what is known as 'regenerative medicine' - growing new tissue to replace diseased tissue in sick individuals.

"With the advances made at the CSIR, Africa is now set to benefit from this new and powerful technology."

Inducing adult cells to revert to stem cells

According to the council, Dr Janine Scholefield, one of the CSIR researchers involved in generating iPSCs, had recorded video footage of rhythmically beating cells through a microscope.

"The beating pattern is distinctive, and easily recognisable as heart muscle cells," the CSIR said. "These cells, however, didn't come from a heart, but were, instead, transformed into heart cells, from skin cells taken from an adult.

"This is the basis of iPSC technology, which induces adult cells (like skin cells) to revert back into stem cells, which are cells at the earliest stage of life. These early stem cells can then be programmed to become any type of adult cell, such as skin, heart, brain and blood cells."

Vast medical possibilities

The medical possibilities of iPSCs are vast, and include growing new tissue for transplanted into people suffering from various diseases.

"It could be used for restoring sight by replacing defective tissue in the eye; transplanting new heart muscle cells into people with serious heart diseases; giving people with anaemia new healthy blood cells; even harnessing brain cells to treat disorders such as Parkinson's disease," the CSIR said.

Another way of harnessing the technology is to create "disease-in-a-dish" models, by growing diseased tissue from the stem cells of sick patients.

"Since stem cells can be made from a patient's own cells, the cells contain the exact same genetic characteristics as the patient these were taken from, meaning that this tissue will be 'sick' in the same way as the patient."

Avoiding ethical controversies

Part of the novelty of the technology lies in the fact that stem cells can be made from almost any individual with almost any disease, simply by taking a skin sample from that person.

Another benefit of using iPSCs is that they bypass the ethical controversy surrounding classical stem cells, which must be taken from embryos.

Scholefield will be collaborating with Professor Susan Kidson at the University of Cape Town Medical School in developing her models, allowing for the testing of possible cures, or understanding the disease, without having to subject a patient to invasive surgery or untested trial medication.

Applying cutting-edge research in Africa

Scholefield spent three years working with international experts at Oxford University in the UK in order to perfect the technique of creating iPSCs. She now forms part of a team of CSIR scientists with expertise in various emerging health technologies, who work to apply this knowledge in an African context.

According to Dr Musa Mhlanga, who heads up the CSIR's gene expression and biophysics group, cutting-edge medical research "is not useful to Africa if knowledge is being created and applied only in the developed world.

"Given the high disease burden in Africa, our aim is to create knowledge, as well as be innovators and expert practitioners, of the newest and best technologies."

Mhlanga's group receives long-term financial support from the Department of Science and Technology.

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In Treatment of Child’s Heart Defect, Doctors Find a Stem-Cell Surprise

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By Ron Winslow

Doctors at Yale University have successfully implanted a biodegradable scaffold seeded with a four-year-old girl’s own bone-marrow cells to help treat a serious heart defect, asWSJ’s Heartbeat column describes.

The tube — about three inches long — is  made of polyester material similar to that used in the manufacture of dissolvable sutures. Six months after Angela Irizarry’s surgery, it had disappeared, replaced by a bioengineered conduit that acts like a normal blood vessel.

The vanishing act for the scaffold was expected, but what happens to the cells, including stem cells, that spawned the new vessel?

Much to the researchers’ surprise, says Chris Breuer, the Yale pediatric surgeon leading the experimental tissue-engineering project, the cells go away too.

Stem cells and certain other bone-marrow cells have building-block properties that make them the foundation for more specialized cells that grow into the body’s various tissues and structures. Researchers have long believed that stem cells transplanted into heart tissue, for instance, would be a primary component of whatever new tissue that grew as a result.

“A lot of people think that when you put cells in, they turn into whatever cells you want them to turn into,” Breuer tells the Health Blog. “We’ve clearly shown that doesn’t happen in our graft.”

Indeed, in experiments performed to learn how the tubes morphed into blood vessels, Breuer and his colleagues transplanted their scaffold seeded with human cells into mice bred with deficient immune systems to prevent rejection of the cells.  Within a few days, the human cells were gone, replaced within the scaffold by mouse cells, including cells characteristic of those that line the inner wall of blood vessels.

Initially, “I refused to believe it,” Breuer says. “I redid the experiment three different ways and saw the same thing every time.”

The upshot: Transplanted cells that have a quality of stem cells don’t build new parts themselves, he says. ”They cause the body to induce regeneration.”

Whether the same process happens in human patients such as Angela isn’t certain, he says. But the finding is consistent with other research that sheds new light on how the power of stem cells may be marshaled to regenerate tissue and body parts affected by birth defects, injury and disease.