Stem cell stories that caught our eye: How Zika may impact adult brains; Move over CRISPR there’s a new kid in town; How our bodies store fat

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.

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Zika mosquito

Zika virus could impact adult brains

It’s not just a baby’s developing brain that is vulnerable to the Zika virus, adult brains may be too. A new study shows that some stem cells that help repair damage in the adult brain can be impacted by Zika. This is the first time we’ve had any indication this could be a problem in a fully developed brain.

The study, in the journal Cell Stem Cell, looked at neural progenitors, a  stem cell that plays an important role in helping replace or repair damaged neurons, or nerve cells, in the brain. The researchers exposed the cells to the Zika virus and found that it infected the cells, causing some of the cells to die, and also limited the ability of the cells to proliferate.

In an interview in Healthday, Sujan Shresta, a researcher at the La Jolla Institute for Allergy and Immunology and one of the lead authors of the study, says although their work was done in adult mice, it may have implications for people:

“Zika can clearly enter the brains of adults and can wreak havoc. But it’s a complex disease, it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle and now we know what to look for.”

Move over CRISPR, there’s a new gene-editing tool in town

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Jennifer Lopez: Photo courtesy MTV

For much of the last year the hottest topic in stem cell and gene editing research has been CRISPR and the ease with which it can be used to edit genes. It’s so hot that apparently it’s the title of an upcoming TV show starring Jeniffer Lopez.

But hold on J-Lo, a new study in Nature Communications says by the time the show is on the air it may be old hat. Researchers at Carnegie Mellon and Yale University have developed a new gene-editing system, one they claim is easier to use and more accurate than CRISPR. And to prove it, they say they have successfully cured a genetic blood disorder in mice, using a simple IV approach.

Tools like CRISPR use enzymes to cut open sections of DNA to edit a specific gene. It’s like using a pair of scissors to cut a piece of string that has a big knot in the middle; you cut out the knot then join the ends of the string together. The problem with CRISPR is that the enzymes it uses are quite large and hard to use in a living animal – let alone a human – so they have to remove the target cells from the body and do the editing in the lab. Another problem is that CRISPR sometimes cuts sections of DNA that the researchers don’t want cut and could lead to dangerous side effects.

Greater precision

The Carnegie Mellon/Yale team say their new method avoids both problems. They use nanoparticles that contain molecules made from peptide nucleic acid (PNA), a kind of artificial form of DNA. This PNA is engineered to be able to cut open DNA and bind to a specific target without cutting anything else.

The team used this approach to target the mutated gene in beta thalassemia, a blood disorder that can be fatal if left untreated. The therapy binds to the malfunctioning gene, enabling the body’s own DNA repair system to correct the problem.

In a news story in Science Daily Danith Ly, one of the lead authors on the study, says even though the technique was successful in editing the target genes just 7 percent of the time, that is way more than the 0.1 percent rate most other gene editing tools achieve.

“The effect may only be 7 percent, but that’s curative. In the case of this particular disease model, you don’t need a lot of correction. You don’t need 100 percent to see the phenotype return to normal.”

Hormone that controls if and when fat cells mature

Obesity is one of the fastest growing public health problems in the US and globally. Understanding the mechanisms behind how that happens could be key to finding ways to address it. Now researchers at Stanford University think they may have uncovered an important part of the answer.

Their findings, reported in Science Signaling, show that mature fat cells produce a hormone called Adamts1 which acts like a switch for surrounding stem cells, determining if they change into fat-storing cells.   People who eat a high-fat diet experience a change in their Adamst1 production, and that triggers the nearby stem cells to specialize and start storing fat.

There are still a lot of questions to be answered about Adamst1, including whether it acts alone or in conjunction with other as yet unknown hormones. But in an article in Health Canal, Brian Feldman, the senior author of the study, says they can now start looking at potential use of Adamst1 to fight obesity.

“That won’t be a simple answer. If you block fat formation, extra calories have to go somewhere in the body, and sending them somewhere else outside fat cells could be more detrimental to metabolism. We know from other researchers’ work that liver and muscle are both bad places to store fat, for example. We do think there are going to be opportunities for new treatments based on our discoveries, but not by simply blocking fat formation alone.”

 

Stem cell stories that caught our eye: a surprising benefit of fasting, faster way to make iPSCs, unlocking the secret of leukemia cancer 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.

Fasting

Is fasting the fountain of youth?

Among the many insults our bodies endure in old age is a weakened immune system which leaves the elderly more susceptible to infection. Chemotherapy patients also face the same predicament due to the immune suppressing effects of their toxic anticancer treatments. While many researchers aim to develop drugs or cell therapies to protect the immune system, a University of Southern California research report this week suggests an effective alternative intervention that’s startlingly straightforward: fasting for 72 hours.

The study published in Cell Stem Cell showed that cycles of prolonged fasting in older mice led to a decrease in white blood cells which in turn set off a regenerative burst of blood stem cells. This restart of the blood stem cells replenished the immune system with new white blood cells. In a pilot Phase 1 clinical trial, cancer patients who fasted 72 hours before receiving chemotherapy maintained normal levels of white blood cells.

A look at the molecular level of the process pointed to a decrease in the levels of a protein called PKA in stem cells during the fasting period. In a university press release carried by Science Daily, the study leader, Valter Longo, explained the significance of this finding:

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the ‘okay’ for stem cells to go ahead and begin proliferating and rebuild the entire system. And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

In additional to necessary follow up studies, the team is looking into whether fasting could benefit other organ systems besides the immune system. If the data holds up, it could be that regular fasting or direct targeting of PKA could put us on the road to a much more graceful and healthier aging process.

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Faster, cheaper, safer way to use iPS cells

Science, like traffic in any major city, never moves quite as quickly as you would like, but now Japanese researchers are teaming up to develop a faster, and cheaper way of using iPSC’s , pluripotent stem cells that are reprogrammed from adult cells, for transplants.

Part of the beauty of iPSCs is that because those cells came from the patient themselves, there is less risk of rejection. But there are problems with this method. Taking adult cells and turning them into enough cells to treat someone can take a long time. It’s expensive too.

But now researchers at Kyoto University and three other institutions in Japan have announced they are teaming up to change that. They want to create a stockpile of iPSCs that are resistant to immunological rejection, and are ready to be shipped out to researchers.

Having a stockpile of ready-to-use iPSCs on hand means researchers won’t have to wait months to develop their own, so they can speed up their work.

Shinya Yamanaka, who developed the technique to create iPSCs and won the Nobel prize for his efforts, say there’s another advantage with this collaboration. In a news article on Nikkei’s Asian Review he said these cells will have been screened to make sure they don’t carry any potentially cancer-causing mutations.

“We will take all possible measures to look into the safety in each case, and we’ll give the green light once we’ve determined they are sound scientifically. If there is any concern at all, we will put a stop to it.”

CIRM is already working towards a similar goal with our iPSC Initiative.

Unlocking the secrets of leukemia stem cells

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Zombies: courtesy “The Walking Dead”

Any article that has an opening sentence that says “Cancer stem cells are like zombies” has to be worth reading. And a report in ScienceMag  that explains how pre-leukemia white blood cell precursors become leukemia cancer stem cells is definitely worth reading.

The article is about a study in the journal Cell Stem Cell by researchers at UC San Diego. The senior author is Catriona Jamieson:

“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves. What’s more, we found a method to dial it down.”

An enzyme called ADAR1 is known to spur cancer growth by manipulating small pieces of genetic material known as microRNA. Jamieson and her team wanted to track how that was done. They discovered it is a cascade of events, and that once the first step is taken a series of others quickly followed on.

They found that when white blood cells have a genetic mutation that is linked to leukemia, they are prone to inflammation. That inflammation then activates ADAR1, which in turn slows down a segment of microRNA called let-7 resulting in increased cell growth. The end result is that the white blood cells that began this cascade become leukemia stem cells and spread an aggressive and frequently treatment-resistant form of the blood cancer.

Having uncovered how ADAR1 works Jamieson and her team then tried to find a way to stop it. They discovered that by blocking the white blood cells susceptibility to inflammation, they could prevent the cascade from even starting. They also found that by using a compound called 8-Aza they could impede ADAR1’s ability to stimulate cell growth by around 40 percent.

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Catriona Jamieson – definitely not a zombie

Jamieson says the findings open up all sorts of possibilities:

“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression. In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”

This wasn’t a CIRM-funded study but we have supported other projects by Dr. Jamieson that have led to clinical trials.