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Scientists Get Closer to the Stem Cells That May Drive Cancers

By Stem Cell Medicine

THURSDAY, May 15, 2014 (HealthDay News) -- Although the very concept of cancer stem cells has been controversial, new research provides proof that these distinct types of cells exist in humans.

Using genetic tracking, researchers found that a gene mutation tied to cancer's development can be traced back to cancer stem cells. These cells are at the root of cancer and responsible for supporting the growth and progression of the disease, the scientists report.

Cancer stem cells are able to replenish themselves and produce other types of cancer cells, just as healthy cells produce other normal cells, the study's British and European authors explained.

"It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back," study first author Dr. Petter Woll, of the MRC Weatherall Institute for Molecular Medicine at the University of Oxford, said in a university news release.

The researchers, led by a team of scientists at Oxford and the Karolinska Institute in Sweden, said their findings could have significant implications for cancer treatment. They explained that by targeting cancer stem cells, doctors could not only get rid of a patient's cancer but also prevent any remaining cancer cells from sustaining the disease.

The study, published May 15 in Cancer Cell, involved 15 patients diagnosed with myelodysplastic syndromes (MDS), a type of cancer that often develops into acute myeloid leukemia, a form of blood cancer.

The researchers examined the cancer cells in the patients' bone marrow. Four of the patients were also monitored over time. One patient was followed for two years. Two patients were followed for 30 months and another patient was monitored for 10 years.

According to the researchers, in prior studies citing the existence of cancer stem cells, the lab tests that were used to identify these cells were considered by many to be unreliable.

However, "In our studies we avoided the problem of unreliable lab tests by tracking the origin and development of cancer-driving mutations in MDS patients," explained study leader Sten Eirik Jacobsen, of Oxford's MRC Molecular Haematology Unit and the Weatherall Institute for Molecular Medicine.

According to the research, a distinct group of MDS cells had all the characteristics of cancer stem cells, and only these particular cancer cells appeared able to cause tumor spread.

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Scientists Get Closer to the Stem Cells That May Drive Cancers

Herpes-loaded stem cells used to kill brain tumors

By Stem Cell Clinic

Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs) -- a type of stem cell that gives rise to bone marrow tissue -- which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

"So, how do you translate this into the clinic?" asked Shah, who also is an Associate Professor at Harvard Medical School.

"We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking," he continued. "So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors."

Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. "Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers' solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma -- this time created from brain tumor cells that were resistant to the herpes virus -- the therapy led to increased animal survival.

"Our approach can overcome problems associated with current clinical procedures," Shah said. "The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors."

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Herpes-loaded stem cells used to kill brain tumors

Successful Stem Cell Therapy in Monkeys is First of Its Kind

By Uncategorized

Mice have been poked, prodded, injected and dissected in the name of science. But there are limits to what mice can teach us especially when it comes to stem cell therapies. For the first time, researchers haveturned skin cells into bone in a creature more closely related to humans: monkeys.

In a study published Thursday in the journal Cell Reports, scientists report that they regrew bone in 25rhesus macaques using induced pluripotent stem cells (iPSCs) taken from the creatures skin. Since macaques are more closely related to humans, their discovery could help push stem cell therapies into early clinical trials in humans.

While this is the good news, the bad news is that iPSCs can also seed tumors in monkeys; however, the tumors grew at a far slower rate than in previous studies in mice. This finding further emphasizes the key role primates likely will play in testing the safety of potential stem cell therapies.

Repairing Bone

Researchers used a common procedure to reprogram macaque skin cells, and coaxed them into pluripotent cells that were capable of building bone. They seeded these cells into ceramic scaffolds, which are already used by surgeons used to reconstruct bone. The cells took, and the monkeys successfully grew new bone.

In some experiments, the monkeys formed teratomas nasty tumors that can contain teeth and hair when they were injected with undifferentiated iPSCs, or cells that have the potential to change into any kind of cell. However, the tumors grew 20 times slower than in mice, highlighting an important difference between mice and monkeys.

Fortunately, tumors did not form in monkeys that were injected with differentiated iPSCs, or cells that were programmed to createbone cells.

Advancing Research

Researchers say their successful procedure proves that monkeys willplay an important rolein research on therapies using iPSCs. These monkeys will help scientists test and analyze risks associated with the therapies and improve their safety.

Originally posted here:
Successful Stem Cell Therapy in Monkeys is First of Its Kind

Researchers: Dose of measles puts womans cancer into remission

By Stem Cell Clinic

A woman with an incurable cancer is now in remission, thanks, doctors say, to a highly concentrated dose of the measles virus.

For 10 years, Stacy Erholtz, 49, battledmultiple myeloma, a deadly cancer of the blood.

Doctors at the Mayo Clinic say she had received every type of chemotherapy drug available for her cancer and had undergone two stem cell transplants, only to relapse time and again.

Then researchers gave her and five other multiple myeloma patients a dose of a highly concentrated, lab-engineered measles virus similar to the measles vaccine.

In fact, the dose Erholtz received contained enough of the virus to vaccinate approximately 100 million people.

The idea here is that a virus can be trained to specifically damage a cancer and to leave other tissues in the body unharmed, said the lead study author, Dr. Stephen Russell.

Its a concept known as virotherapy and its been done before.

Mayo Clinic scientists say thousands of cancer patients have been treated with viruses but this is the first case of a patient with a cancer that had spread throughout the body going into remission.

Erholtz was cancer-free for nine months.

I think we succeeded because we pushed the dose higher than others have pushed it, Russell said. And I think that is critical. The amount of virus thats in the bloodstream really is the driver of how much gets into the tumors.

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Researchers: Dose of measles puts womans cancer into remission

Succssful Stem Cell Therapy in Monkeys is First of Its Kind

By Uncategorized

Mice have been poked, prodded, injected and dissected in the name of science. But there are limits to what mice can teach us especially when it comes to stem cell therapies. For the first time, researchers haveturned skin cells into bone in a creature more closely related to humans: monkeys.

In a study published Thursday in the journal Cell Reports, scientists report that they regrew bone in 25rhesus macaques using induced pluripotent stem cells (iPSCs) taken from the creatures skin. Since macaques are more closely related to humans, their discovery could help push stem cell therapies into early clinical trials in humans.

While this is the good news, the bad news is that iPSCs can also seed tumors in monkeys; however, the tumors grew at a far slower rate than in previous studies in mice. This finding further emphasizes the key role primates likely will play in testing the safety of potential stem cell therapies.

Repairing Bone

Researchers used a common procedure to reprogram macaque skin cells, and coaxed them into pluripotent cells that were capable of building bone. They seeded these cells into ceramic scaffolds, which are already used by surgeons used to reconstruct bone. The cells took, and the monkeys successfully grew new bone.

In some experiments, the monkeys formed teratomas nasty tumors that can contain teeth and hair when they were injected with undifferentiated iPSCs, or cells that have the potential to change into any kind of cell. However, the tumors grew 20 times slower than in mice, highlighting an important difference between mice and monkeys.

Fortunately, tumors did not form in monkeys that were injected with differentiated iPSCs, or cells that were programmed to createbone cells.

Advancing Research

Researchers say their successful procedure proves that monkeys willplay an important rolein research on therapies using iPSCs. These monkeys will help scientists test and analyze risks associated with the therapies and improve their safety.

Link:
Succssful Stem Cell Therapy in Monkeys is First of Its Kind

First test of pluripotent stem cell therapy in monkeys is a success

By Uncategorized

PUBLIC RELEASE DATE:

15-May-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Researchers have shown for the first time in an animal that is more closely related to humans that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys reported in the Cell Press journal Cell Reports on May 15th also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

"We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute. "We have used this model to demonstrate that tumor formation of a type called a 'teratoma' from undifferentiated autologous iPSCs does occur; however, tumor formation is very slow and requires large numbers of iPSCs given under very hospitable conditions. We have also shown that new bone can be produced from autologous iPSCs, as a model for their possible clinical application."

Autologous refers to the fact that the iPSCs capable of producing any tissue typein this case bonewere derived from the very individual that later received them. That means that use of these cells in tissue repair would not require long-term or possibly toxic immune suppression drugs to prevent rejection.

The researchers first used a standard recipe to reprogram skin cells taken from rhesus macaques. They then coaxed those cells to form first pluripotent stem cells and then cells that have the potential to act more specifically as bone progenitors. Those progenitor cells were then seeded onto ceramic scaffolds that are already in use by reconstructive surgeons attempting to fill in or rebuild bone. And, it worked; the monkeys grew new bone.

Importantly, the researchers report that no teratoma structures developed in monkeys that had received the bone "stem cells." In other experiments, undifferentiated iPSCs did form teratomas in a dose-dependent manner.

The researchers say that therapies based on this approach could be particularly beneficial for people with large congenital bone defects or other traumatic injuries. Although bone replacement is an unlikely "first in human" use for stem cell therapies given that the condition it treats is not life threatening, the findings in a primate are an essential step on the path toward regenerative clinical medicine.

"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity," Dunbar said. "The testing of human-derived cells in vitro or in profoundly immunodeficient mice simply cannot model these crucial preclinical safety and efficiency issues."

Excerpt from:
First test of pluripotent stem cell therapy in monkeys is a success

Stem Cell Therapy Shows Promise for MS in Mouse Model

By Uncategorized

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Newswise LA JOLLA, CAMay 15, 2014Mice crippled by an autoimmune disease similar to multiple sclerosis (MS) regained the ability to walk and run after a team of researchers led by scientists at The Scripps Research Institute (TSRI), University of Utah and University of California (UC), Irvine implanted human stem cells into their injured spinal cords.

Remarkably, the mice recovered even after their bodies rejected the human stem cells. When we implanted the human cells into mice that were paralyzed, they got up and started walking a couple of weeks later, and they completely recovered over the next several months, said study co-leader Jeanne Loring, a professor of developmental neurobiology at TSRI.

Thomas Lane, an immunologist at the University of Utah who co-led the study with Loring, said he had never seen anything like it. Weve been studying mouse stem cells for a long time, but we never saw the clinical improvement that occurred with the human cells that Dr. Loring's lab provided, said Lane, who began the study at UC Irvine.

The mices dramatic recovery, which is reported online ahead of print by the journal Stem Cell Reports, could lead to new ways to treat multiple sclerosis in humans.

"This is a great step forward in the development of new therapies for stopping disease progression and promoting repair for MS patients, said co-author Craig Walsh, a UC Irvine immunologist.

Stem Cell Therapy for MS

MS is an autoimmune disease of the brain and spinal cord that affects more than a half-million people in North America and Europe, and more than two million worldwide. In MS, immune cells known as T cells invade the upper spinal cord and brain, causing inflammation and ultimately the loss of an insulating coating on nerve fibers called myelin. Affected nerve fibers lose their ability to transmit electrical signals efficiently, and this can eventually lead to symptoms such as limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression.

Current therapies, such as interferon beta, aim to suppress the immune attack that strips the myelin from nerve fibers. But they are only partially effective and often have significant adverse side effects. Lorings group at TSRI has been searching for another way to treat MS using human pluripotent stem cells, which are cells that have the potential to transform into any of the cell types in the body.

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Stem Cell Therapy Shows Promise for MS in Mouse Model

First test of pluripotent stem cell therapy in monkeys is successful

By Uncategorized

Researchers have shown for the first time in an animal that is more closely related to humans that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys reported in the Cell Press journal Cell Reports on May 15th also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

"We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute. "We have used this model to demonstrate that tumor formation of a type called a 'teratoma' from undifferentiated autologous iPSCs does occur; however, tumor formation is very slow and requires large numbers of iPSCs given under very hospitable conditions. We have also shown that new bone can be produced from autologous iPSCs, as a model for their possible clinical application."

Autologous refers to the fact that the iPSCs capable of producing any tissue typein this case bonewere derived from the very individual that later received them. That means that use of these cells in tissue repair would not require long-term or possibly toxic immune suppression drugs to prevent rejection.

The researchers first used a standard recipe to reprogram skin cells taken from rhesus macaques. They then coaxed those cells to form first pluripotent stem cells and then cells that have the potential to act more specifically as bone progenitors. Those progenitor cells were then seeded onto ceramic scaffolds that are already in use by reconstructive surgeons attempting to fill in or rebuild bone. And, it worked; the monkeys grew new bone.

Importantly, the researchers report that no teratoma structures developed in monkeys that had received the bone "stem cells." In other experiments, undifferentiated iPSCs did form teratomas in a dose-dependent manner.

The researchers say that therapies based on this approach could be particularly beneficial for people with large congenital bone defects or other traumatic injuries. Although bone replacement is an unlikely "first in human" use for stem cell therapies given that the condition it treats is not life threatening, the findings in a primate are an essential step on the path toward regenerative clinical medicine.

"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity," Dunbar said. "The testing of human-derived cells in vitro or in profoundly immunodeficient mice simply cannot model these crucial preclinical safety and efficiency issues."

The NIH team is now working with collaborators on differentiation of the macaque iPSCs into liver, heart, and white blood cells for eventual clinical trials in hepatitis C, heart failure, and chronic granulomatous disease, respectively.

Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.

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First test of pluripotent stem cell therapy in monkeys is successful

Human stem cell treatment helps mice with MS-like condition walk again

By Stem Cell Treatment

Home > News > world-news

Washington, May 16 : Mice severely disabled by a condition that was similar to multiple sclerosis (MS) were able to walk less than two weeks following treatment with human neural stem cells.

In striking contrast to active, healthy mice, those with an MS-like condition must be fed by hand because they cannot stand long enough to eat and drink on their own. When scientists transplanted human neural stem cells into the MS mice, they expected no benefit from the treatment. They thought the mice would reject the cells, much like rejection of an organ transplant.

Co-senior author, Tom Lane, Ph.D., a professor of pathology at the University of Utah, said my postdoctoral fellow Dr. Lu Chen came to me and said, 'The mice are walking.' I didn't believe her.

He began the study with co-first author Chen at the University of California, Irvine.

Within a remarkably short period of time, 10 to 14 days, the mice had regained motor skills. Six months later, they showed no signs of slowing down.

The findings have been published online in the journal Stem Cell Reports.

--ANI (Posted on 16-05-2014)

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