Category Archives: Diseases

ScienceDaily (Oct. 25, 2012) When the era of regenerative medicine dawned more than three decades ago, the potential to replenish populations of cells destroyed by disease was seen by many as the next medical revolution. However, what followed turned out not to be a sprint to the clinic, but rather a long tedious slog carried out in labs across the globe required to master the complexity of stem cells and then pair their capabilities and attributes with specific diseases.

In a review article appearing October 25 in the journal Science, University of Rochester Medical Center scientists Steve Goldman, M.D., Ph.D., Maiken Nedergaard, Ph.D., and Martha Windrem, Ph.D., contend that researchers are now on the threshold of human application of stem cell therapies for a class of neurological diseases known as myelin disorders -- a long list of diseases that include conditions such as multiple sclerosis, white matter stroke, cerebral palsy, certain dementias, and rare but fatal childhood disorders called pediatric leukodystrophies.

"Stem cell biology has progressed in many ways over the last decade, and many potential opportunities for clinical translation have arisen," said Goldman. "In particular, for diseases of the central nervous system, which have proven difficult to treat because of the brain's great cellular complexity, we postulated that the simplest cell types might provide us the best opportunities for cell therapy."

The common factor in myelin disorders is a cell called the oligodendrocyte. These cells arise, or are created, by another cell found in the central nervous system called the glial progenitor cell. Both oligodendrocytes and their "sister cells" -- called astrocytes -- share this same parent and serve critical support functions in the central nervous systems.

Oligodendrocytes produce myelin, a fatty substance that insulates the fibrous connections between nerve cells that are responsible for transmitting signals throughout the body. When myelin-producing cells are lost or damaged in conditions such as multiple sclerosis and spinal cord injury, signals traveling between nerves are weakened or even lost. Astrocytes also play an essential role in the brain. Long overlooked and underappreciated, it is now understood that astrocytes are critical to the health and signaling function of oligodendrocytes as well as neurons.

Glial progenitor cells and their offspring represent a promising target for stem cell therapies, because -- unlike other cells in the central nervous system -- they are relatively homogeneous and more readily manipulated and transplanted. In the case of oligodendrocytes, multiple animal studies have shown that, once transplanted, these cells will disperse and begin to repair or "remyelinate" damaged areas.

"Glial cell dysfunction accounts for a broad spectrum of diseases, some of which -- like the white matter degeneration of aging -- are far more prevalent than we previously realized," said Goldman. "Yet glial progenitor cells are relatively easy to work with, especially since we don't have to worry about re-establishing precise point to point connections as we must with neurons. This gives us hope that we may begin to treat diseases of glia by direct transplantation of competent progenitor cells."

Scientists have reached this point, according to the authors, because of a number of key advances. Better imaging technologies -- namely advanced MRI scanners -- now provide greater insight and clarity into the specific damage caused in the central nervous system by myelin disorders. These technologies also enable scientists to precisely follow the results of their work.

Even more importantly, researchers have overcome numerous obstacles and made significant strides in their ability to manipulate and handle these cells. Goldman's lab in particular has been a pioneer in understanding the precise chemical signals necessary to coax stem cells into making glial progenitor cells, as well as those needed to "instruct" these cells to make oligodendrocytes or astrocytes. His lab has been able to produce these cells from a number of different sources -- including "reprogramming" skin cells, a technology that has the advantage of genetically matching transplanted cells to the donor. They have also developed techniques to sort these cells based on unique identifying markers, a critical step that ensures the purity of the cells used in transplantation, lowering the risk for tumor formation.

Nedergaard's lab has studied the integration of these cells into existing neural networks, and well as in imaging their structure and function in the adult nervous system. Together, the two labs have developed models of both human neural activity and disease based on animals transplanted with glial progenitor cells, which will enable human neural cells to be evaluated in the context of the live adult brain -- as opposed to a test tube. This work has already opened new avenues in both modeling and potentially treating human glial disease.

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Stem cell therapies for multiple sclerosis, other myelin disorders expected soon

MANILA, Philippines Its supposed to cure various illnesses such as cancer, spinal cord injury and Parkinsons disease. Is stem cell therapy the cure-all that it is touted to be?

Health Undersecretary Teodoro Herbosa said it is important to note that stem cell treatments are still at the experimental stage.

"The advisory is very clear. This is still an investigative form of therapy. Anecdotal reports are not enough evidence to say there is treatment, he said in an interview on ANC's Talkback with Tina Palma.

He said there are only two standard stem cell therapies considered effective and acceptable to the medical community.

"To date, I can only name two cases that are considered standard therapy. That is bone marrow transplantation--one for severe cancer, blood cancer and the other one is bone marrow transplantation after chemotherapy for any type of cancer, he said.

Herbosa said the Department of Health cannot confirm yet if stem cell treatment is indeed effective against certain diseases.

Dr. Tranquilino Elicao Jr., an oncologist who availed of the treatment in April in Frankfurt, Germany, said stem cell therapy cured his high blood pressure, sugar, cholesterol and uric acid.

He had 12 injections of cells, which came from lambs.

After a month, I had my blood tests. Everything went down to normal, Elicao said.

Elicao also said he is not taking medication anymore because he has regained his health.

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Stem cell therapy a cure-all? Not so fast

SANTA BARBARA Biomedical research at UC Santa Barbara has catapulted to a position of leadership in the arena of stem cell biology, offering progress toward cures for vision diseases such as macular degeneration. Stem cell research has the potential to transform the practice of medicine, by replacing diseased tissue with healthy new cells. Interdisciplinary teams of UC Santa Barbara researchers including world-renowned faculty members recruited from the U.S. and Britain are leading the charge. The university's newly renovated lab space is critical to the mission.

The latest research holds the promise of developing stem cells from skin, called induced pluripotent stem cells, which could eventually replace the use of human embryonic stem cells. The hope is to find cures for diseases including macular degeneration, diabetic retinopathy and Alzheimer's.

Campus leaders, dignitaries, scientists, and engineers gathered at UC Santa Barbara on Friday (Oct. 26) to celebrate the completion of a dream: 10,000 square feet of renovated laboratory space devoted to stem cell research. This was the grand opening ceremony and ribbon-cutting in celebration of UC Santa Barbara's Center for Stem Cell Biology and Engineering, part of the Neuroscience Research Institute. The California Institute for Regenerative Medicine (CIRM) contributed to the renovation with a $3.2 million grant that was matched by $3.2 million from the university. The top-flight new laboratories are a magnet for attracting new talent.

Chancellor Henry T. Yang commented: "We think UCSB can make important contributions to stem cell research at the interface of biology, neuroscience, and engineering. The future is very bright as we continue to grow and add more top-notch researchers and faculty to this area. These new laboratories will make this possible."

Kenneth S. Kosik, physician and Harriman Chair in the Department of Molecular, Cellular, and Developmental Biology, and co-director of the Neuroscience Research Institute, remarked on this watershed moment in UCSB's stem cell research. "This is a momentous event," said Kosik. "It's a big milestone for UCSB to have come from a premier engineering institute to a place where we are doing world-class work in another entire area, in stem cell biology. With that triumph, that success, we are moving into world-class ranks here."

Leading stem cell biologist Dennis Clegg, center executive director of strategy, planning and operations, and co-principal director of the California Project to Cure Blindness, has directed the center since its inception, and also directed strategy for UC Santa Barbara's specific contribution to stem cell biology.

"We realized that we have a tremendous collection of expertise in bioengineering, basic molecular biology, and neuroscience," said Clegg. "Those groups together, working together collaborating across normal interdisciplinary lines make for a powerful combination of expertise. And we've been able to address some of the key problems in stem cell research, like how to deliver the cells, how to get the cells pure, how to monitor the cells after transplantation, using this combination of bioengineering and molecular biology.

"This has been a long process to complete this renovation for the stem cell center," Clegg said. "It started back in 2007, with our application to CIRM for a major facilities grant. It involved a large number of people on campus scientists, design and construction, administrators.

"We spent many hours figuring out how to come up with matching funds and how to raise money for the stem cell center. It really is a realization of our dream to expand stem cell research on campus. We think we have a lot more to offer. The trajectory is upward; we are really making progress. This will allow us to hire new people, new faculty, bring them in and collaborate with the group of stellar scientists that we've already assembled."

One of the new center directors, Peter Coffey, was hired with a CIRM recruitment grant earlier this year. Coffey, who holds the Garland Chair and is the center's executive director of translation, is considered a star in the world of stem cell science. While at the University College London, he started a group called the London Project to Cure Blindness, which will begin clinical trials early next year. Coffey hopes to bring a part of this project to California.

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New lab space for stem cell research

A Cambridge University technology team that developed a way to generate liver cells from skin cells has formed a new company to supply stem cell products to the drug discovery and regenerative medicine sectors.

DefiniGEN is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and global stem cell guru Professor Roger Pedersen of the Anne McLaren Laboratory of Regenerative Medicine.

DefiniGEN is based in Cambridge and has been funded by a group led by Cambridge Enterprise, the Universitys commercialisation arm, along with members of Cambridge Angels and Cambridge Capital Group.

Prof Pedersen is one of the coveted brains of stem cell research. He moved to Cambridge to escape a puritan US approach to stem cell research and has resisted attempts to woo him back across the Atlantic.

The potential therapeutic applications of stem cells such as regenerating damaged tissues or organs have generated a great deal of interest over the past decade. While these types of applications are exciting, it is a long journey from lab to clinic.

The most immediate impact of stem cells on human health will most likely come from their use in the development of new drugs. The ability to generate stem cells by reprogramming cells from patients skin has revolutionised human stem cell research.

These cells, known as human induced pluripotent stem cells (hIPSC), can be differentiated into almost any cell type, allowing the opportunity to have a ready source of human cells for testing new therapies.

DefiniGEN has developed the technology to generate human liver cells (hepatocytes) in a highly reproducible and scalable manner for commercial use. This represents a major breakthrough in the costly and time-consuming process of developing new therapies.

The technology has also been used to effectively model a diverse range of inherited liver diseases and has the potential to accelerate the development of new therapies for these conditions.

The liver is the key organ for metabolising drugs and removing toxins from the body. Consequently, it is often affected by toxic compounds.

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Pedersen creates stem cell drug powerhouse

ScienceDaily (Oct. 15, 2012) A new method of using adult stem cells as a model for the hereditary condition Gaucher disease could help accelerate the discovery of new, more effective therapies for this and other conditions such as Parkinson's, according to new research from the University of Maryland School of Medicine.

Scientists at the University of Maryland School of Medicine reprogrammed stem cells to develop into cells that are genetically similar to and react to drugs in a similar way as cells from patients with Gaucher disease. The stem cells will allow the scientists to test potential new therapies in a dish, accelerating the process toward drug discovery, according to the paper published online in the journal the Proceedings of the National Academy of Sciences (PNAS) on Oct. 15.

"We have created a model for all three types of Gaucher disease, and used stem cell-based tests to evaluate the effectiveness of therapies," says senior author Ricardo Feldman, Ph.D., associate professor of microbiology and immunology at the University of Maryland School of Medicine, and a research scientist at the University of Maryland Center for Stem Cell Biology and Regenerative Medicine. "We are confident that this will allow us to test more drugs faster, more accurately and more safely, bringing us closer to new treatments for patients suffering from Gaucher disease. Our findings have potential to help patients with other neurodegenerative diseases as well. For example, about 10 percent of Parkinson's disease patients carry mutations in the recessive gene for Gaucher disease, making our research possibly significant for Parkinson's disease as well."

Gaucher disease is the most frequent lipid-storage disease. It affects 1 in 50,000 people in the general population. It is most common in Ashkenazi Jews, affecting 1 in 1,000 among that specific population. The disease occurs in three subtypes -- Type 1 is the mildest and most common form of the disease, causing symptoms such as enlarged livers and spleens, anemia and bone disease. Type 2 causes very serious brain abnormalities and is usually fatal before the age of two, while Type 3 affects children and adolescents.

The condition is a recessive genetic disorder, meaning that both parents must be carriers for a child to suffer from Gaucher. However, said Dr. Feldman, studies have found that people with only one copy of a mutated Gaucher gene -- those known as carriers -- are at an increased risk of developing Parkinson's disease.

"This science is a reflection of the mission of the University of Maryland School of Medicine -- to take new treatments from bench to bedside, from the laboratory to patients, as quickly as possible," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "We are excited to see where this research goes next, bringing new hope to Gaucher patients and their families."

Dr. Feldman and his colleagues used the new reprogramming technology developed by Shinja Yamanaka in Japan, who was recognized with this year's Nobel Prize for Medicine or Physiology. Scientists engineered cells taken from the skin of Gaucher patients, creating human induced pluripotent stem cells, known as hiPSC -- stem cells that are theoretically capable of forming any type of cell in the body. Scientists differentiated the cells to form white blood cells known as macrophages and neuronal cells.

A key function of macrophages in the body is to ingest and eliminate damaged or aged red blood cells. In Gaucher disease, the macrophages are unable to do so -- they can't digest a lipid present in the red blood cell membrane. The macrophages become engorged with lipid and cannot completely clear the ingested red blood cells. This results in blockage of membrane transport pathways in the macrophages lodged in the bone marrow, spleen and liver. The macrophages that the scientists created from the reprogrammed stem cells exhibited this characteristic hallmark of the macrophages taken from Gaucher patients.

To further test the stem cells, the scientists administered a recombinant enzyme that is effective in treating Gaucher patients with Type 1 disease. When the cells were treated with the enzyme, the function of the macrophages was restored -- they completely cleared the red blood cells.

"The creation of these stem cell lines is a lovely piece of stem cell research," said Curt Civin, M.D., professor of pediatrics and physiology, associate dean for research and founding director of the Center for Stem Cell Biology & Regenerative Medicine at the University of Maryland School of Medicine. "Dr. Feldman is already using these Gaucher patient-derived macrophages to better understand the disease fundamentals and to find novel medicines for Gaucher disease treatment. A major goal of our Center for Stem Cell Biology & Regenerative Medicine is to translate our fundamental discoveries into innovative and practical clinical applications that will enhance the understanding, diagnosis, treatment, and prevention of many human diseases. Clinical applications include not only transplantation of stem cells, but also the use of stem cells for drug discovery as Dr. Feldman's studies so beautifully illustrate."

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Stem cell model for hereditary disease developed

With all the publicity about the miraculous effects of stem cell therapy, the Department of Health (DOH) should prepare itself for the possibility that the new procedure would be performed by unqualified, and completely clueless, people.

I passed a beauty parlor recently and saw a huge poster on its door announcing the arrival of stem cell therapy. I was instantly reminded of botched breast enhancement and nose jobs performed by salon personnel who seemed to think it was as easy to learn complicated surgical procedures as it was to train to cut hair or do manicures and pedicures.

The DOH should start warning the public not to fall for these special offers just because they are available at giveaway rates.

Modern lifestyle problem

Experts have repeatedly talked about problems brought about by modern lifestyles. Changing diets and stress are two of the best known. Dr. Jaime G. Ignacio, section chief of gastroenterology at Veterans Hospital and head of the Digestive Malignancy Council of the Philippine Society of Gastroenterology, said constipation could be one of the consequences of the combination of these two factors.

Speaking at an event hosted by Boehringer Ingelheim, maker of Dulcolax (generic name Bisacodyl), a formulation for constipation relief, Ignacio, who, as a gastroenterologist is a specialist in digestive system disorders, defined the problem as having fewer than three bowel movements in a week (normal ranges from three times a week to three times a day).

He said constipation itself was not a disease but it could sometimes be a symptom of something serious, like colorectal cancer. But he said about 95 percent of cases were acuteoccurring suddenly and lasting for only a short periodresulting from some sudden lifestyle or hormonal changes, the taking of medication, lack of exercise, etc.

Ignacio said acute was easy to treat, with products like Dulcolax to solve the problem. But, if left unattended, acute constipation could lead to a chronic or long-term condition, which was the more worrisome, and would need medical attention.

He said constipation should be treated as soon as the problem had lasted for four or more days.

Constipation is part of modern living. [Like other diseases] prevention is the key. Safe and effective treatment is available [if needed], Ignacio stressed.

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Beauty salon ‘offers’ stem cell therapy