Stem cell stories that caught our eye: Zika virus and adult brains, a step toward precision medicine and source of blood stem cells

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.

Zika virus and the adult brain.  While almost all the press attention for the Zika virus has centered on pregnant women and the devastating impact the virus can have on their developing babies, a few stories have noted that while most adults don’t know they have been infected, a few do. The one significant impact seen is a relatively rare incidence of Guillain-Barre Syndrome, which can cause temporary partial paralysis. That has triggered a few researchers to look for other impacts in adults infected with the mosquito-borne virus.

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Researchers trying to understand why the virus leads to the underdeveloped brains known as microcephaly, in infants have shown the virus does its nasty work at the level of the nerve stem cell. Although adults have far fewer nerve stem cells than a developing fetus, they do have some. So a team at Rockefeller University in New York and the La Jolla Institute for Allergy and Immunology decided to look for any effects of infection on adult nerve stem cells in mice.  They published the work this week in the journal Cell Stem Cell and report a dramatic reduction in adult nerve stem cells in infected mice.

“Adult neurogenesis is implicated in learning and memory,” said the La Jolla Institute’s Sujan Shresta in a press release from the journal. “We don’t know what this would mean in terms of human diseases, or if cognitive behaviors of an individual could be impacted after infection.”

Mice are normally resistant to Zika infection, so the researchers first had to genetically engineer mice to be susceptible to infection. That means several layer of caveats and more research are needed before any assertions about adult impact of Zika infection in humans.

This work captured considerable press attention including in Buzzfeed, NBC and USNews and World Report.

 

Heart felt precision medicine.  With the boost of a special initiative launched by the Obama administration, precision medicine is becoming all the rage, at least as a goal. While a few cancer therapies currently use this concept of matching therapies to a specific patient’s genetic makeup, few doctors outside of oncology can turn to similarly precise therapies.

Cardio cells image

Heart muscle cells

Work from a CIRM-funded team at Stanford has moved other doctors a bit closer to this goal for heart disease. But this research will not lead to treating it, rather it could allow doctors to prevent therapies used for other diseases from causing heart disease. Joseph Wu and his team have made two discoveries that help validate the use of the iPS reprogramming technique to make patient-specific stem cells and then mature them into heart muscle cells and see how those cells react to specific drugs.

“Thirty percent of drugs in clinical trials are eventually withdrawn due to safety concerns, which often involve adverse cardiac effects,” said Wu in a press release picked up by ScienceNewsLine. “This study shows that these cells serve as a functional readout to predict how a patient’s heart might respond to particular drug treatments and identify those who should avoid certain treatments.”

 

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Joseph Wu

There has always been some concern that the genetic manipulation used to create iPS cells changes the genetics of any adult tissue you make from the cells. So, with samples from three patients who were undergoing heart biopsy or transplant, which allowed harvesting mature heart muscle, the team compared the genetic signature of the adult heart muscle and that of heart muscle created from iPS cells.  They found no significant differences.

With skin samples from another seven subjects they created iPS cells and then heart muscle and compared their genetic signatures. The found some slight difference in all seven, but dramatic differences in one. That difference was in a genetic pathway involved in the inner workings of heart muscle. When they treated those cells with a diabetes drug that had been linked to heart problems, the cells reacted quite differently from the cells of the other six subjects treated with the same drug. With this knowledge a doctor could avoid ever choosing to put that particular patient on that diabetes drug.

 

Source of blood stem cells matters.  For years, bone marrow transplant—the one currently routine stem cell therapy—required digging into someone bone to harvest the stem cells. Over the decades that the procedure has been saving thousands of lives doctors have found less invasive methods to get the stem cells using drugs to “mobilize” the marrow stem cells and get them to move into the blood stream where they can be harvested.

While stem cell donors often find the new procedure a vast improvement, no one had done a thorough review of the outcomes for patients who receive stem cells gathered by the different procedures until a paper this week from the Fred Hutchison Cancer Research Center in Seattle. While they did not find any differences in overall life expectancy, they found vastly different outcomes in quality of life including psychological wellbeing and ability to return to work.

The Hutchison team attributed most of this difference to a lower rate of Graft Versus Host Disease (GVHD), possibly the most dangerous side effect of the procedure, which occurs when the stem cell transplant also contains adult immune system cells from the donor and those “graft” cells attack the “host,” the patient. It makes sense that when you harvest cells from the blood stream you would be more likely to also capture mature immune cells than when you harvest cells from marrow. And GVHD can be extremely painful, debilitating, and often deadly.

Stephanie Lee Hutchison

Stephanie Lee

“When both your disease and the recommended treatment are life-threatening, I don’t think people are necessarily asking ‘which treatment is going to give me better quality of life years from now?'” said Stephanie Lee the lead author in a press release from the cancer center. “Yet, if you’re going to make it through, as many patients do, you want to do it with good quality of life. That’s the whole point of having the transplant.”

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