Cancer-killing stem cells engineered in lab

Brain tumours are often solid and hard to reach so stem cells are an effective way of targeting them

Brain tumours are often solid and hard to reach so stem cells are an effective way of targeting them

By Shaun Gibson @ShaunyNews

Scientists from Harvard Medical School have discovered a way of turning stem cells into killing machines to fight brain cancer.

There may soon be a new way to use stem cells in the fight against brain cancer. A team has created a way to genetically engineer stem cells so that they can produce and secrete tumor-killing toxins that 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.  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.

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). Credit: Khalid Shah, MS, PhD

“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 Harvard neuroscientist Khalid Shah, MS, PhD, 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. Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs.”

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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Second life: Scientists ‘reset’ human stem cells to ‘blank state’

I think this is an amazing breakthrough by Science, but I fear the religious crowd will but an end to it, even if it does save lives, to reset stem cells could see people with brain illness’s and people disabled like me having a better or normal life. I hope it gets the go ahead Worldwide.

Scientists have learned to “reset” human stem cells to their earliest state. This breakthrough gives hope for millions of people suffering from incurable conditions, like Parkinson’s Disease, as scientists hope their success would lead to cures. British and Japanese scientists have managed to reboot stem cells to the state equivalent 7 to 10-day old embryo, before it implants in the womb. “These cells may represent the real starting point for formation of tissues in the human embryo,” said Austin Smith, director of the Britain’s Cambridge Stem Cell Institute, who co-led the research.“Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues.” Studying the reset cells could lead to a better understanding of human development and how embryo development can go wrong, cause miscarriages and developmental disorders. “We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people,” Smith said.

In the future, this knowledge could allow the production of safe and more reproducible starting materials for a wide range of applications including cell therapies, scientists said in the study, published in Cell Journal.  Until now it was only possible to produce what in scientific language is called pluripotent stem cells in the lab either from cells extracted from a very early stage embryo or from adult cells that have been induced into a pluripotent state. Human pluripotent stem cells are first of all valuable because of their unique capability to become any of the cells and tissues in the body.

However, scientists have been trying to generate human pluripotent stem cells that are truly pristine (also known as naïve). Before they succeeded, researchers have only been able to derive cells that are slightly further down the developmental pathway, not a totally “blank slate,” scientists say. What happened now is that British and Japanese scientists have managed to induce a ground state by rewiring the genetic circuitry in human embryonic and induced pluripotent stem cells, the University of Cambridge explains. It is much easier to control the process of generating stem cells in mouse cells which can be frozen in a state in their naïve or “blank state” using a protein called LIF. But this is not the case with human cells, which are not as responsive to LIF. That means they require different control, involves switching key genes on and off.

For this reason scientists have been unable to generate human pluripotent cells that are as primitive or as consistent as mouse embryonic stem cells. To avoid this problem, the scientists introduced two genes – NANOG and KLF2 – which caused a network of genes controlling the cell to reboot and induce the early pluripotent state. So now, those “reset cells” share many of the characteristics of authentic naïve embryonic stem cells isolated from mice, suggesting that they represent the earliest stage of development. “Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest and show subtle differences between the individual cells. It’s as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of others,” Smith said.

Experts say that by helping to regenerate tissue, stem cell science could offer new ways of treating conditions for which there are currently no cures – including heart and eye diseases, Parkinson’s and strokes. But there is still a lot of research required. “We now need to carry out further studies to establish how our cells compare with others,” said Yasuhiro Takashima, of the Japan Science and Technology Agency, who worked with Smith. “We don’t yet know whether these will be a better starting point than existing stem cells for therapies, but being able to start entirely from scratch could prove beneficial.”