Novel Mutiple Sclerosis Stem Cell Study Begins

Physorg

A small group of patients with multiple sclerosis were enrolled in a new pilot clinical trial to test bone marrow stem cell therapy at Frenchay Hospital. The aim of the trial is to find out what effects, good or bad, it has on patients with MS, and their disability. It is being conducted by the University of Bristol and North Bristol NHS Trust.

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

Until now, patients have not been treated in this manner, but laboratory studies in Bristol and elsewhere have worked with similar cells to determine potential benefits to aid repair in multiple sclerosis.

The trial is being led by the University of Bristol and Neil Scolding who is a Professor of Clinical Neurosciences for North Bristol NHS Trust.

He said: “We believe this form of adult stem cell treatment, carried out in collaboration with colleagues in the Bone Marrow Transplant Unit at the BRI, will be safe and well-tolerated but, because patients with MS have never had this treatment before, safety has to be proven before any further studies of larger numbers of patients can take place.”

“We will therefore be monitoring this small number of patients extremely carefully over the next 9-12 months. Provided, as is envisaged, we do not find serious adverse effects, we hope to raise the funds to undertake a larger study to examine the effectiveness of such treatment in MS.”

To determine general fitness and degree of disability from MS, patients meeting the initial entry criteria were assessed in the Neurology department and the Burden Centre at Frenchay Hospital.

Frenchay and also at The Hammersmith Hospital in London, various types of brain scans were conducted. Then the patients underwent bone marrow collection under a short general anesthetic at the Bone Marrow Transplant Unit at the BRI.

Via a vein in the arm, the stem cells are delivered back to the patient later the same day after they have been processed from the marrow.

A range of various monitoring tests and scans at Frenchay and in London are then carried out over the following weeks and months.

Stem Cell Breakthrough for Huntington’s Disease

There may be new hope for individuals suffering from Huntington’s disease — a fatal disorder for which there is currently no cure or even a treatment to slow the disease. A new avenue of research has been opened by scientists who were sparked by an odd biological phenomenon: how a canary learns a new song.

Stem-cell therapy might someday be used to treat the disease according to scientists at the University of Rochester Medical Center. The Journal of Clinical Investigation published their paper on September 20th.

In the brains of mice affected by a form of Huntington’s, the team used gene therapy to guide the development of endogenous stem cells. Many more new, viable brain cells as well as significantly longer and healthier lives characterized the treated mice. This was in stark contrast to the their non-treated counterparts.

Neurologist Steven Goldman, M.D., Ph.D., the lead author of the study said that the study offers a new approach in the fight against Huntington’s, but that it is too early to predict whether such a treatment might work in people. The knowledge of the defective gene hasn’t yet translated to better care for patients despite scientists being aware of the gene for more than a decade.

“There isn’t much out there right now for patients who suffer from this utterly devastating disease,” said Goldman, who is at the forefront developing new techniques to try to bring stem-cell therapy to the bedside of patients. “While the promise of stem cells is broadly discussed for many diseases, it’s actually conditions like Huntington’s — where a very specific type of brain cell in a particular region of the brain is vulnerable — that are most likely to benefit from stem-cell-based therapy.”

The lead authors of the latest paper are former post-doctoral associate Sung-Rae Cho, Ph.D., now at Yonsei University in South Korea, and Abdellatif Benraiss, Ph.D., research assistant professor at the University of Rochester Medical Center.

The latest results have their roots in research Goldman did more than 20 years ago as a graduate student at Rockefeller University. Goldman discovered that every time a canary learns a new song, it creates new brain cells called neurons. He was doing basic neuroscience studies and investigating how exactly canaries learn new songs. His doctoral thesis opened the door to the possibility that the brain has a font of stem cells that could serve as the source for new cells. His 1983 thesis was also the first report of neurogenesis — the production of new brain cells — in the adult brain.

The finding led to a career for Goldman, who has created ways to isolate stem cells. Goldman’s group has learned how to re-create signals to direct the cells’ development. These molecular signals that help determine what specific types of cells they become were also discovered by Goldman thanks to their innovative techniques.

Benraiss has worked closely with Goldman for more than 10 years on the Huntington’s project.

“The type of brain cell that allows a canary to learn a new song is the same cell type that dies in patients with Huntington’s disease,” said Goldman, professor of Neurology, Neurosurgery, and Pediatrics, and chief of the Division of Cell and Gene Therapy. “Once we worked out the molecular signals that control the development of these brain cells, the next logical step was to try to trigger their regeneration in Huntington’s disease.”

Affecting about 30,000 people in the United States, Huntington’s is an inherited disorder. The condition results in depression, irritability, cognitive difficulties, problems with coordination, and involuntary movements. These symptoms can be contributed to a defective gene which results in the death of vital brain cells known as medium spiny neurons. When patients reach their 30′s or 40′s, the young to mid adulthood range, symptoms usually begin to appear. The disease is fatal and their is currently no way to slow the progression of the disease.

Scientists must learn the extensive molecular signaling that shapes their development before stem cells can be used to replace neurons lost in Huntington’s and almost any disease. In the brain, a stem cell might become a medium spiny neuron or a dopamine-producing neuron to replace the cells destroyed by Huntington’s or Parkinson’s. However, the fate of the stem cells depends on a tremendous number of biochemical signals.

To replace those that had become defective in mice with the disease, Goldman’s team set up a one-two molecular punch as a recipe for generating new medium spiny neurons. Extra copies of two genes were carried into a region of the mouse brain called the ventricular wall, which is home to stem cells. This was achieved by using a cold virus known as adenovirus. The neostriatum, which is affected by Huntington’s disease, is very close to the ventricular wall which was the final destination for the stem cells.

To help stop stem cells from becoming another type of cell in the brain, an astrocyte, extra copies of a gene called Noggin were used. To help the stem cells to become neurons, they also put in extra copies of the gene for BDNF (brain-derived neurotrophic factor). Basically, stem cells were bathed in a brew that had extra Noggin and BDNF to direct their development into medium spiny neurons.

The results were dramatic in the mice which had a severe form of Huntington’s disease. Compared to no new neurons in mice that weren’t treated, several thousand newly formed medium spiny neurons were observed in the neostriatum when the treatment mice were examined. The treated mice were more coordinated, active, and healthier for a significantly longer period of time compared to the untreated mice. They lived about 17 percent longer compared to the untreated mice.

The experiment was designed to test the idea that scientists could generate new medium spiny neurons in an organism where those neurons had already become sick. Goldman is working on ways to extend the duration of the improvement now that the capability has been demonstrated. Treatment in patients is the ultimate goal for the future.

“This offers a strategy to restore brain cells that have been lost due to disease. That could perhaps be coupled with other treatments currently under development,” said Goldman. Many of those treatments are being studied at the University, which is home to a Huntington’s Disease Center of Excellence and is the base for the Huntington Study Group.

In addition to Benraiss, Cho, and Goldman, other authors include former Cornell graduate student Eva Chmielnicki, Ph.D.; Johns Hopkins neurosurgeon Amer Samdani, M.D., now at Shriners Children’s Hospital in Philadelphia; and Aris Economides of Regeneron Pharmaceuticals. The work was funded by the National Institute of Neurological Disorders and Stroke, the Hereditary Disease Foundation, and the High Q Foundation.

Stem Cell’s at the Heart of Bioartificial Liver

The successful removal of ammonia, a highly toxic by-product which causes brain damage, coma, and even death, and the production of urea was announced today by HepaLife Technologies, Inc. They developed a first-of-its-kind artificial liver device where the company’s patented PICM-19 liver stem cells were placed inside its proprietary artificial liver device to produce the positive results.

“Today’s results demonstrate that, while inside our bioartificial liver device, HepaLife’s PICM-19 cells are able to produce substantial amounts of urea and remove toxic ammonia, while remaining healthy, and replicating important liver-like functions,” stated Mr. Frank Menzler, President and CEO of HepaLife. “This is a significant achievement that marks a major milestone in the development of our artificial liver device.”

“These new results have certainly exceeded our early performance expectations of the HepaLife bioartificial liver design. Our goal is to now further evaluate the HepaLife bioartificial liver system in-vitro and in-vivo, and continue to move closer to an application with the Food and Drug Administration for our cell-based device.”

Similar to the functions mimicked by HepaLife’s PICM-19 cells in today’s research outcomes, the biological cells inside the device which are responsible for truly replicating and performing the functions of the human liver are the most vital component of the artificial liver device, not the actual mechanical hardware say researchers.

Over the entire duration of the study, the system successfully produced significant amounts urea and liver-specific protein such as albumin while removing toxic ammonia confirmed research data from experiments with the PICM-19 cells inside HepaLife’s artificial liver device. Reaching peak levels at termination of the study after two weeks, the production of urea and albumin increased over time, marking the most important outcome of the study.

Since cells which are not contact-inhibited tend to become cancerous, an important indicator if normal cell growth was that the PICM-19 liver cells remained contact-inhibited. This confirmed earlier findings in observations of cell replication and growth. The HepaLife’s PICM-19 cells inside its liver device system remained non-tumorigenic.

An indication of the cells’ physical form and structure was observed in the same test. Normal morphology was displayed as the HepaLife’s PICM-19 liver stem cells successfully differentiated into hepatocytes (liver cells).

Researchers analyzed levels of lactate and glucose — indicators of metabolic function — alongside oxygen and carbon dioxide, respectively, when evaluating the chemical function and overall health of the PICM-19 liver cells inside HepaLife’s bioartificial liver system. Throughout the duration of the studies, these monitored levels remained favorably within targeted parameters in all cases.

“These results suggest that HepaLife’s bioartificial liver system is an artificially created, ‘living biosystem’ — our goal from the early beginning — with cells that behave as we have long desired for our artificial liver device,” concluded Mr. Menzler.

Intended for the treatment of liver failure, the HepaLife(TM) Bioartificial Liver device consists of three basic components: (1), the HepaDrive(TM), a perfusion system for pumping the patient’s plasma through the bioreactor while controlling gas supply and temperature for best possible performance of the cells; (2)the bioreactor, a unit filled with PICM-19 cells which biologically mimic the liver’s function; and (3) a plasma filter, separating the patient’s blood into blood plasma and blood cells.

HepaLife is developing the first-of-its-kind bioartificial liver while incorporating the PICM-19 cell line. Designed to operate outside the patient’s body HepaLife’s bioartificial liver is currently under development. The bioartificial liver processes the patient’s blood-plasma by removing toxins, enhancing metabolic function, and ultimately, imitates the liver’s natural function.

The bioartificial liver is envisioned to mimic important functions of the human liver by circulating the patient’s blood inside the device, where it is exposed to HepaLife’s patented PICM-19 liver stem cells.

Bone Marrow Stem Cell Slow Down Liver Damage

Using stem cells taken from the bone marrow, scientists have developed a new way to treat liver failure by dampening the immune response.

The technique could help save human lives after it moves past animal testing.

Potentially, the liver would be given the maximum chance to repair itself as the patient could be kept alive longer until a donor organ is found. The journal PLOS One featured the work by The Massachusetts General Hospital.

With the ability to regenerate itself, the liver is one of the few major organs with this ability.

But diseases like chronic hepatitis, or excessive long-term alcohol consumption stress the organ to point that is too extensive to cope with.

Powerful drugs to suppress the immune response are required to avoid transplant rejection of donor organs — this is necessary for the only current treatment for severe “end stage” damage. But still, donor organs themselves are limited.

External liver assist devices have successfully supported some patients, but such machines require a supply of (preferably) human liver cells, which have been difficult to acquire.

Tissues supporting blood cell development in the marrow cavity can be created using stem cells from bone marrow. The mesenchymal stem cells (MSCs) were used be the United States researchers.

By putting a brake on the movement of immune cells to areas of damage, previous research has shown that MSCs are able to inhibit several immune system activities.

MSC’s can be expanded to levels that could be therapeutically useful after being extracted from a patient’s own bone marrow.

To treat rats with liver failure, the researchers tested several ways of using the cells.

Simply transplanting MSCs into the animals’ livers was not effective.

However, lessening inflammation and halting cell death were two methods of delivering molecules secreted by the cells.

Also, greatly reducing signs of liver failure in the animals, and boosted survival rates from 14% to 71%, was the result of cycling the blood of rats with liver failure through an external bioreactor containing MSCs.

To try to halt cell damage, and allow the organ to regenerate, a patient could be injected with a drug containing MSC-derived molecules in theory said researcher Biju Parekkadan.

A device similar to the bioreactor could be considered to buy extra time before a transplant if the initial efforts with the drug were not successful, or the damage was too extensive.

The research is still in an early stage warned the British Liver Trust.

But Professor Mark Thursz, of St Mary’s Hospital, London and spokesperson for the trust, said: “A long standing goal in hepatology is the suppression of liver cell death until regeneration could occur.”

“This development could potentially reduce the number of donor organs used in urgent transplant procedures thereby increasing the number available for the growing number of patients on routine waiting lists.”

Novel Multiple Sclerosis Stem Cell Study Begins

A small group of patients with multiple sclerosis were enrolled in a new pilot clinical trial to test bone marrow stem cell therapy at Frenchay Hospital. The aim of the trial is to find out what effects, good or bad, it has on patients with MS, and their disability. It is being conducted by the University of Bristol and North Bristol NHS Trust.

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

Until now, patients have not been treated in this manner, but laboratory studies in Bristol and elsewhere have worked with similar cells to determine potential benefits to aid repair in multiple sclerosis.

The trial is being led by the University of Bristol and Neil Scolding who is a Professor of Clinical Neurosciences for North Bristol NHS Trust.

He said:

Stem Cell Therapy for Skin

Concentrating on the latest discoveries in skin science and regenerative medicine, Paris hosted Stem Cells and the Skin last week. The event marked the 7th such symposium for LVMH Research.

Scientists from Europe and the United States were invited to discuss the latest developments in stem cell therapy and its possible benefits to skin care. French luxury consumer group Louis Vuitton Moet Hennessy used its research arm to organize the event.

Stem cells are at the heart of organ development and tissue repair because they have the potential to differentiate into different and specialized cells.

For a range of degenerative conditions and injuries such as premature baldness, severe burns, and more serious conditions such as heart disease and Parkinson’s; stem cell treatment promises benefits. Recent findings in therapeutic applications and the advances in stem cell research for the science of the skin were explored and implications discussed at LVMH’s symposium.

Cedric Blanpain’s work on the characterization, activation and differentiation of the epidermal stem cell was presented. Blanpain works at the Interdisciplinary Research Institute, at Free University of Brussels, in Belgium.

Residing in a portion of the hair follicle called the bulge, special multipotent follicular stem cells were the focus of Blanpain’s research. Real therapeutic benefits may come form these cells in the future because of their multipotency; the fact that they can divide into many different cell types.

To help pinpoint the processes that lead to hair regeneration, the project isolates the bulge stem cells, and investigates the optimal conditions for in vitro clonal analyses.

Additionally, a presentation entitled ‘Epidermal Basal Layer: the Regenerative Stem Cell Skin Compartment’ was given by Carlo Pincelli, from the Institute of Dermatology, at the University of Moderna and Reggio Emilia, in Modena, Italy.

Pincelli’s work focuses on investigating the biochemicals that help to regulate the survival and division of the stem cells, which reside on the basal layer of the skin in between the hair follicles.

The protein survivin and high levels of a transmembrane receptor called beta1-integrin were isolated by Pincelli and his team. These two components appear to be important for the division and differentiation of the stem cells.

For the treatment of skin disorders and burns, stem cell therapy could be used for therapeutic purposes. Improved knowledge of how the skin renews itself and how the stem cells function highlight this fact.

Concentrating on the possibility of in-vivo ‘reconstructed’ skin, a concept which LVMH feels would have powerful implications for our ageing society was the final discussion of the symposium. The catalyst was the question “The reconstructed man, a probable future?” by Eric Perrier, the Executive Vice President of LVMH’s R&D center.

Umbilical Cord Blood is a Lifesaver

A friend informed us about the option of donating umbilical cord blood to a public cord blood bank when my wife was pregnant with our second child two years ago. We made the potentially life-saving donation and were thrilled to celebrate our daughter

Woman Cancer Free – Adult Stem Cell at Work

It’s seems unusual to say that someone would be renewing themselves near the age of 70, but that is just what Dixie Sisk did.

The Mercer County mother and grandmother decided it was time to try a controversial, cutting-edge treatment that could give her a chance at living cancer-free. She had already endured and survived through repeated rounds of chemotherapy, and 89 radiation treatments during her 11 year bought with cancer.

Sisk, with the hopes of seeing her grandchildren grow up, agreed to the stem cell transplant. However, her doctors were skeptical of her chance for success.

Thalassemia and Sickle Cell Disease can be Cured with Cord Blood Stem Cells

Umbilical cord blood taken from a compatible sibling can cure children with Thalassemia and Sickle Cell Disease. The report was made by the Children’s Hospital & Research Center Oakland and ViaCell, Inc.

Cord blood from a relative may have advantages over bone marrow transplantation and can be an effective source of stem cells for transplantation in children affected with Sickle Cell Disease and Thalassemia. The research was presented by Dr. Mark Walters, Director of the Blood and Marrow transplant program at Children’s Hospital & Research Center Oakland. Dr. Walters made the presentation at the Sickle Cell Disease Association of America and National Institutes of Health (NIH) 35th Annual Convention.

“Patients with Sickle Cell and Thalassemia often lead debilitating lives,” said Dr. Walters. “Through continued research and transplant success, sibling umbilical cord blood has proven to be effective in curing children of these blood disorders. I expect the use of umbilical cord blood will continue to increase and as we gain more experience using cord blood stem cells in transplant medicine, I believe it could outpace the use of bone marrow in transplant medicine.”

The data presented at the Sickle Cell Disease Association of America and NIH meeting showed outcomes from children treated under The Sibling Connection Program, a directed sibling transplant program implemented by ViaCord and Children’s Hospital Oakland Research Institute (CHORI), the research arm of Children’s Hospital & Research Center Oakland.

More than 100 children have been treated with cord blood thanks to the program. 23 children were transplanted for Thalassemia and 17 were transplanted for Sickle Cell Disease under the Sibling Connection Program. The median age of patients treated for Sickle Cell Disease was 8 years and 5 years for patients treated for Thalassemia.

Clinical advantages over bone marrow have been demonstrated in regards to sibling umbilical cord blood transplantation in young children. A reduction in the common side effect and leading cause of death in transplant medicine, graft-versus-host (GvHD), was also observed. GvHD was observed in six of the Sickle Cell Disease patients, but none of them developed chronic GvHD. As for Thalassemia, none of the patients were observed to have acute or chronic GvHD.

For patients treated for Sickle Cell Disease, the median time to platelet recovery (greater than 20,000 per microliter) and neutrophil recovery (ANC greater than 500 cells per microliter) was 36 days and 18 days respectively.

82% of the patients treated for Sickle Cell Disease survived and is disease-free. For patients treated for Thalassemia, the median time to platelet recovery (greater than 20,000 per microliter) and neutrophil recovery (ANC greater than 500 cells per microliter) was 47 days and 25 days respectively. 91% of the patients treated for Thalassemia are now disease free and 96% of the patients survived.

The Sibling Connection Program in the area of directed transplants for sibling donor umbilical cord blood was formed in 2006 by the combined efforts of CHORI and ViaCell. Units of cord blood that has been collected and processed through the program have treated over 100 children to date. This includes transplants through cord blood stored through CHORI’s Sibling Donor Cord Blood Program and cord blood collected, preserved and stored with ViaCord. If a family has a child diagnosed with a condition that can be treated with a cord blood stem cell transplant and they meet the other requirements of the program, the Sibling Connection Program provides ViaCord’s comprehensive cord blood collection, processing and five years of storage at no cost.

Resulting in the red blood cells being a sickle or crescent shape, Sickle Cell Disease is an inherited blood disorder. Tissue damage is caused when the abnormally shaped cells prevent normal flow of oxygen to tissues by becoming rigid. Anemia, jaundice, frequent infections, and chest pain are among the common symptoms. No universal cure for Sickle Cell Disease currently exists.

Blood transfusions, antibiotics, intravenous fluids, pain management, and even surgery are currently used to treat complications associated with Sickle Cell Disease. Over 80,000 people in the United States have sickle cell anemia and over 2.5 million carry the trait. People of Mediterranean descent and African Americans are the two demographics that Sickle Cell Disease predominantly effects. National Sickle Cell Awareness Month is September.

Umbilical cord blood is an emerging therapeutic treatment option for patients with Thalassemia and Sickle Cell Disease. In 2000, the first cord blood unit was released by ViaCord to treat Sickle Cell Disease. Families who have children affected with Sickle Cell Disease make up 30% of all enrollments in the ViaCord/CHORI Sibling Connection Program.

Hemoglobin is a critical oxygen-carrying protein in red blood cells. The decreased production of hemoglobin is what characterizes Thalassemia which is another hereditary blood disorder. A shortage of red blood cells occurs along with anemia. Lifelong red blood cell transfusions and the resulting complications come with a diagnosis that usually occurs in early childhood. Poor growth, enlarged spleen and liver, anemia, jaundice, and abnormal facial bones are some of the symptoms of the condition. However, the symptoms of Thalassemia due vary depending on the type and severity of the disease. There are approximately 1,000 people are living with Thalassemia in the U.S. and an estimated 2 million people in the United States carry the genetic trait for Thalassemia.

With proven therapeutic effect in treating over 40 diseases, umbilical cord blood is a valuable, non-controversial source of stem cells. Certain blood disorders such as sickle cell anemia, thalassemia and other genetic disorders, bone marrow failure syndromes such as Diamond Blackfan anemia and severe aplastic anemia, and cancers such as Non-Hodgkin’s lymphoma and Acute Lymphoblastic Leukemia (ALL) can be treated. To date, nearly 8,000 cord blood transplants have been performed world wide. A significantly higher survival rate has been observed when umbilical cord blood transplants from a family member, rather than from a non-relative are used.

Stem Cells from Testicles – Another Non-Controversial Breakthrough

Stem cell taken from men’s testicles could be transformed into a wide range of tissue types to help fight disease. United States researchers have come up with a new use for the rich source of stem cells.

The cells were reprogrammed to be heart cells, blood vessels, and other tissues after scientists isolated and extracted them form the testes of male mice.

Cancer, heart disease, strokes, Parkinson’s disease and other conditions could all be treated if the results can be duplicated using in humans. The ethical concerns surrounding embryonic stem cells would also be negated by this breakthrough.

Shahin Rafii continued to work long and hard on the project since the testes provide such a potentially rich source of stem cells. He spent years working and now the payoff is evident. Rafii is a doctor at Weill Cornell Medical College in New York.

“Testes are designed to generate a lot of sperm and they have these germ cells,” he said.

“So germ cells are designed also in a way to give us two different tissues as well so we were able to get a germ cell from testes and instruct them to become other tissues.”

Humans will also benefit because the results are transferable to humans said Dr. Rafii.

“It can easily be applied to a human in near future,” he said.

Subjects should not be difficult to find Rafii added.

“If I had end stage heart disease, I would think, take all my testes, all right? So it is a no-brainer,” he said.

The journal Nature has published Dr. Rafii’s research.

While the work is promising it will be some time before the results could be reproduced in humans said Peter Schofield, who is the executive director of the Prince of Wales Medical Research Institute in Sydney.

“I think there’s still quite a bit of experimental work to be done,” he said.

“The mouse experiments used a number of techniques which are possible in mouse embryology but would not in any way be translatable to potential human treatment today.”

“But the important thing is that the experiments showed was that it was possible.”

Creating non-embryonic stem cells carries a high level of interest says Professor Schofield.

“Certainly the comments that came out from the researchers’ labs in the United States perhaps are a little bit over-selling around the potential benefits of adult versus embryonic stem cells,” he said.

“I guess the situation here in Australia is that both of them are now permitted under various strong licensing regimes and the technology that delivers the clinical benefits will obviously be the one that works.”

“This is really important research because it shows that there is another possible way of reprogramming adult stem cells. In the mouse it shows that those cells were able to form important other organs.”

“There’s still a lot of steps before that could be done in a human situation, but the fact that it has been done is both very exciting and offers a lot of promise.”

For men, it is a possible breakthrough that will manifest itself in the future. But women should not be disappointed either says Dr. Rafii. They will also benefit.

“In women also this stem cell exists but the number is very, very low and we hope that eventually we can be able to get these stem cells from their ovaries as well,” he said.

“Also another point – some men can give stem cells to compatible, genetically compatible females so it still can be applied for women as well.”