Harvard Stem Cell Institute scientists at Massachusetts General Hospital have devised a new way to use stem cells in the fight against brain cancer. A team led by neuroscientist Khalid Shah, MS, PhD, who recently demonstrated the value of stem cells loaded with cancer-killing herpes viruses, now has a way to genetically engineer stem cells so that they can produce and secrete tumor-killing toxins.

In the AlphaMed Press journal Stem Cells, Shah's team shows how the toxin-secreting stem cells can be used to eradicate cancer cells remaining in mouse brains after their main tumor has been removed. The stem cells are placed at the site encapsulated in a biodegradable gel. This method solves the delivery issue that probably led to the failure of recent clinical trials aimed at delivering purified cancer-killing toxins into patients' brains. Shah and his team are currently pursuing FDA approval to bring this and other stem cell approaches developed by them to clinical trials.

"Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don't work as well in solid tumors because the cancers aren't as accessible and the toxins have a short half-life," said Shah, who directs the Molecular Neurotherapy and Imaging Lab at Massachusetts General Hospital and Harvard Medical School.

"A few years ago we recognized that stem cells could be used to continuously deliver these therapeutic toxins to tumors in the brain, but first we needed to genetically engineer stem cells that could resist being killed themselves by the toxins," he said. "Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs."

Cytotoxins are deadly to all cells, but since the late 1990s, researchers have been able to tag toxins in such a way that they only enter cancer cells with specific surface molecules; making it possible to get a toxin into a cancer cell without posing a risk to normal cells. Once inside of a cell, the toxin disrupts the cell's ability to make proteins and, within days, the cell starts to die.

Shah's stem cells escape this fate because they are made with a mutation that doesn't allow the toxin to act inside the cell. The toxin-resistant stem cells also have an extra bit of genetic code that allows them to make and secrete the toxins. Any cancer cells that these toxins encounter do not have this natural defense and therefore die. Shah and his team induced toxin resistance in human neural stem cells and subsequently engineered them to produce targeted toxins.

"We tested these stem cells in a clinically relevant mouse model of brain cancer, where you resect the tumors and then implant the stem cells encapsulated in a gel into the resection cavity," Shah said. "After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models of resected brain tumors."

Shah next plans to rationally combine the toxin-secreting stem cells with a number of different therapeutic stem cells developed by his team to further enhance their positive results in mouse models of glioblastoma, the most common brain tumor in human adults. Shah predicts that he will bring these therapies into clinical trials within the next five years.

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Toxin-secreting stem cells treat brain tumors, in mice

In a study that will provide the foundation for scientists to better replicate natural stem cell development in an artificial environment, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Guoping Fan, professor of human genetics, have established a benchmarking standard to assess how culture conditions used to procure stem cells in the lab compare to those found in the human embryo.

The study was published online ahead of print in the journal Cell Stem Cell.

Pluripotent stem cells (PSCs) are cells that can transform into almost any cell in the human body. Scientists have long cultured PSCs in the laboratory (in vitro) using many different methods and under a variety of conditions. Though it has been known that culture techniques can affect what kind of cells PSCs eventually become, no "gold standard" has yet been established to help scientists determine how the artificial environment can better replicate that found in a natural state (in vivo).

Dr. Kevin Huang, postdoctoral fellow in the lab of Dr. Fan and a lead author of the study, analyzed data from multiple existing research studies conducted over the past year. These previously published studies used different culture methods newly developed in vitro in the hopes of coaxing human stem cells into a type of pluripotency that is in a primitive or ground-zero state.

Utilizing recently-published gene expression profiles of human preimplantation embryos as the benchmark to analyze the data, Dr. Huang and colleagues found that culture conditions do affect how genes are expressed in PSCs, and that the newer generation culture methods appear to better resemble those found in the natural environment of developing embryos. This work lays the foundation on the adoption of standardized protocol amongst the scientific community.

"By making an objective assessment of these different laboratory techniques, we found that some may have more of an edge over others in better replicating a natural state," said Dr. Huang. "When you have culture conditions that more consistently match a non-artificial environment, you have the potential for a much better reflection of what is going on in actual human development."

With these findings, Dr. Fan's lab hopes to encourage further investigation into other cell characteristics and molecular markers that determine the effectiveness of culture conditions on the proliferation and self-renewal of PSCs.

"We hope this work will help the research community to reach a consensus to quality-control human pluripotent stem cells," said Dr. Fan.

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Benchmark proposed to better replicate natural stem cell development in the laboratory environment

A team of Harvard Stem Cell Institute researchers at Massachusetts General Hospital has successfully engineered stem cells to produce toxins that can kill cancerous cells, turning them into lethal weapons to in the war against brain tumors. Their study was published online in the journal Stem Cells Friday.

For years, scientists have attempted to create cells that would not only kill cancerous cells but also do it without harming themselves or surrounding healthy cells. The genetically engineered stem cells created by the researchers in Boston were reportedly able to do so, making the development a potential milestone in the field of cancer treatment.

Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs, Khalid Shah, a co-author of the study and the director of the molecular neurotherapy and imaging lab at Massachusetts General Hospital and Harvard Medical School, said in a statement. Cancer-killing toxins have been used with great success in a variety of blood cancers, but they dont work as well in solid tumors because the cancers arent as accessible and the toxins have a short half-life.

Based on experiments conducted on mice, the results were very positive, Shah said. After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells, he said.

Chris Mason, a professor of regenerative medicine at University College London who was not involved in the research, hailed the findings as representative of the future of cancer treatment. This is a clever study, which signals the beginning of the next wave of therapies, Mason told BBC News. It shows you can attack solid tumors by putting minipharmacies inside the patient which deliver the toxic payload direct to the tumor.

However, Nell Barrie, the senior science information manager for Cancer Research UK, told BBC News that much more work is needed to see whether the treatment works on humans. Nonetheless, she said, We urgently need better treatments for brain tumors, and this could help direct treatment to exactly where its needed.

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Scientists Create Toxin Secreting Stem Cells To Fight Brain Tumors

Using stem cells from blood, researchers have been able to grow blood vessels in a week.REUTERS

Researchers at Sahlgrenska University Hospital in Sweden have been successful in transplanting blood vessels made from three spoons of blood.

Two years ago two patients at the hospital received the blood vessels made from stem cellsin the blood.

Earlier, another patient too was treated using blood vessels made by her stem cells but in that case, the researchers had to drill into the bone marrow to obtain the stem cells.

In the later cases, all they needed was three spoons of the patient's blood and a waiting period of a week.

The children did not have the vein that goes from the gastrointestinal tract to the liver. This was rectified using the new blood vessels, a treatment that holds out promise for people with varicose veins and myocardial infarction.

The method also rules out rejection normally accompanying any foreign body transplant.

Professors Olausson and Sumitran-Holgersson have treated three patients so far. Two of the three patients are still doing well and have veins that are functioning well.

They now hope to be able to grow complete organs to overcome organ shortage from donors.

Use of embryonic stem cells to treat macular dystrophy and degeneration has been proven to be safewith low rejection rates.

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Blood Vessels Made from Three Spoons of Blood in a Week's Time

UC San Diego has been named an "alpha clinic" for the clinical study of stem cells, and the distinction comes with $8 million in research grants.

Stem cell therapies represent a new way of treating disease by regenerating damaged tissues and organs. Spokesmen for the UCSD school of medicine say the alpha clinic will focus on clinical trials in humans, not just basic research based on animals.

The decision to make UCSD an alpha clinic was announced Friday by the California Institute for Regenerative Medicine, which was created by California voters after they approved $3 billion for stem cell funding in 2004.

Everything we do has one simple goal, to accelerate the development of successful treatments for people in need, said C. Randal Mills, CIRM president and CEO.

Catriona Jamieson, professor of medicine at UC San Diego School of Medicine, is the alpha clinic grants principal investigator. She said the clinic will provide needed infrastructure for first-in-human stem cell-related clinical trials.

"It will attract patients, funding agencies and study sponsors to participate in, support and accelerate novel stem cell clinical trials and ancillary studies for a range of arduous diseases, Jamieson said.

The university has already announced human stem cell trials, aimed at treating spinal chord injuries, leukemia and type-1 diabetes.

UCSD spokesmen said researchers are conducting those trials using fetal and embryonic stems cells, as well as stem cells made from reprogramming skin cells.

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UCSD Gets $8 Million For Stem Cell Research