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

the-walking-dead-season-6-zombies

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.

Jamieson

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.

 

 

 

 

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