Stem cell stories that caught our eye: more data suggesting iPS cells may be safe, repairing radiation damage, better gene editing and growing organs

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

More evidence suggesting iPS cells safe. Ever since we learned to reprogram adult cells into embryonic-like stem cells called induced Pluripotent Stem Cells (iPSCs) researchers have yearned for the opportunity to try them in patients. At least one patient in Japan has been treated with their own iPSCs, but that project and others have gone slowly because of an equal yearning to make sure the cells are safe and won’t create tumors.

We wrote about a CIRM-funded project published in February that provided some suggestive evidence that iPSCs are safe. That team at The Scripps Research Institute used complex genetic analysis to compare the genetic makeup of the donor adult tissue and the reprogrammed cells. Now, a team in the United Kingdom’s Welcome Trust Sanger Institute have taken a different approach and also produced data suggesting the cells may be safe.

The British team compared changes that occurred with reprogramming of adult blood cells, and the changes that occur when you just grow those adult blood cells in the lab. In fact, mutations occurred 10 times more often in the adult cells and those mutations that did occur in the iPSCs were not in genes related to cancer—the biggest fear with reprogramming.

 “We do not know why this might be – other work has suggested that stem cells have more stringent checks in place than somatic cells, perhaps to maintain the integrity of their genomes.” lead researcher Foad Rouhani told Medical Daily.

 Medical News Today also wrote a story on the research published in PLoS Genetics.

 

Looking small to improve gene therapy. Some of the most promising stem cell clinical trials involve genetic manipulation of the cells to correct a defect or provide a needed protein. While current methods of executing those gene modifications seem to be OK, they are far from perfect. They tend to successfully genetically alter maybe 10 to 15 percent of cells and often kill quite a few cells in the process. Now, a collaboration between two teams in New York seems to have dramatically improved the gene editing rate and the cell survival rate, and they did it with ultra-small structures called nanotubes.

cells on nanotubes

Cells (purple) growing on carbon nanotubes

They grew cells on tiny honeycomb-like disks made up of millions of carbon nanotubes with openings on both sides of the disc. While the researchers at the University of Rochester and the Rochester Institute of Technology (RIT) admit they are not sure how the gene transfer happened, they said the nanotubes seem to form conduits that draw the genes into the cells. In any case the results were surprising—if they can be replicated. Some 85 percent of cells showed the genetic change and 98 percent of the cells survived.

“This represents a very simple, inexpensive, and efficient process that is well-tolerated by cells and can successfully deliver DNA into tens of thousands of cells simultaneously,” said Michael Schrlau of RIT in a story in a university press release picked up by HealthCanal.

The team tested the device with immune cells, stem cells and nerve cells, and had success with each tissue they tried.

 

Stem cell cargo for radiation damage.  Brain tumors stink, not just because of their death rate, but also because the therapy used to try to eradicate them causes debilitating damage itself. Radiation often causes loss of cognitive skills, and in pediatric patients that deficit can continue to get worse years after therapy. In animal models, nerve stem cells have been shown to decrease the damage, but they are difficult to work with and have potential to cause problems of their own.

microvesicles

Microvesicles being secreted from a cell

Researchers at the University of California, Irvine, may have developed a way to garner the stem cell benefit without any downside. The therapeutic effect of the stem cells has been presumed to come largely from various factors they release that reduce inflammation and protect the native nerve cells from damage. So, the Irvine team isolated the cellular components that carry those factors and just injected those packets, called microvesicles, into rats that had been irradiated. When they put those animals through various cognitive tests their performance was as good as rats that had not been irradiated. Radiated but untreated rats did poorly.

“The appeal of strategies using microvesicles instead of stem cells is that they eliminate any concerns for teratoma formation and substantially minimize side effects associated with immunorejection,” said UCI researcher Charles Limoli in a press release picked up by ScienceDaily.

The researchers are now trying to determine exactly which factors in the microvesicles are responsible for preserving the brain tissue. Ars Technica also wrote the story.

 

Growing replacement organs.  Science does not often make it onto the Op/Ed pages of news papers so it was refreshing to see the Los Angeles Times, provide space to Stanford’s Hank Greely to discuss the incredible value of some research that the National Institutes of Health (NIH) will not fund right now. That work would result in growing replacement human organs in pigs.

The research would insert human organ genes into early pig embryos so that as they mature they grow a human organ. NIH placed a moratorium on funding the work last fall and held a work shop on the issue in November. Greely moderated a panel at that workshop and in the Op/Ed stated that the speakers uniformly favored the work. In musing about why the moratorium still stands he said:

“Is the public widely concerned about the welfare of pigs raised to be sacrificed for humans? That’s a tough position for a carnivorous society to take. The bigger source of unease surely has ancient roots, reaching back to chimeras from myth and religion: the sphinx, the Minotaur, and many gods mix species.”

CIRM does fund teams pursuing this potential life saving therapy for the hundreds of people who die waiting on organ transplant lists. These researchers are still in early stages of the work and are not growing any organs at this time.

Another option for replacement organs made its way into the medical literature this week. A US and German team showed that by manipulating the genetics of the pig organs themselves you could make it less likely that the animal organ would be rejected even without trying to turn it into a human organ. My colleague wrote about that work yesterday.

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