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Posts Tagged → stem cells

Sweet Science: Glucose Regulates Stem Cells, Cancer

Most people think of glucose, a humble sugar, as the fuel for several critical body functions, including muscle contraction, brain function, and a host of cellular processes. As it turns out, glucose function might also make a prime target for the development of regenerative medicine and cancer treatments.

Researchers at the Mayo Clinic led by Dr. Andre Terzic report in Cell Metabolism that glucose plays a pivotal role in “re-induction” of pluripotent stem cells (iPSC) from cells called fibroblasts.  These rapidly dividing cells, which normally build connective tissues like collagen, can be convinced to shutter their oxidative, mitochondria-based metabolism in favor of a glycolytic pathway, essentially changing the cells to iPSCs in the process. 

Terzic et al, Cell Metabolism 2011

How does one rewire cellular metabolism?  Expose mouse fibroblasts to a nuclear reprogramming kit (which uses viruses to rewrite nuclear DNA), and then grow them in a high-glucose solution. The scientists used 1H NMR metabolic profiling to monitor changes in cellular metabolism in this sugary environment, finding that in roughly one week they exhibit the same metabolic footprint as embryonic stem cells. No word yet on small molecule drugs that can supplant this process.  
        
In other glycemic news, Stanford Medical School researchers, led by Dr. Amato J. Giaccia, have reported a small molecule capable of inducing “synthetic lethality” in renal cell carcinomas, a common type of kidney cancer. Treatment of cancer by chemical synthetic lethality combines small-molecule inhibition and genetic mutation to selectively kill cancer cells dependent on these pathways.  Carmen briefly covered this advance in the August 8 issue of C&EN.

Two transporters for glucose, GLUT1 and GLUT2, control how kidney cells use sugar; however, genetic mutations cause cancerous cells to favor GLUT1. STF-31, a sulfonamide which targets GLUT1, selectively shuts down glucose transport to those cancerous cells lacking functional VHL tumor suppressor genes, a common mutation in renal cell carcinomas. But tumor cells are notoriously tricky. The Stanford scientists wondered if in the absence of the GLUT1 activity, cancer cells: might simply use an alternative pathway called oxidative phosphorylation to stay alive.  They found that adding excess pyruvate (fuel for the oxidative phosphorylation engine) could not compensate for glucose starvation, and RCC cells still died. Other non-specific glucose transporter inhibitors (fasentin or phloretin, which hit GLUT1 and GLUT2 indiscriminately) killed normal kidney cells as well as cancerous cells, which confirms overexpressed GLUT1 as STF-31’s RCC target.

This Month In Stem Cells

The last month has brought a flurry of activity in the stem cell arena. Here are some selected bits of news for those keeping track:

On September 30th, a Boston-based team led by Harvard Medical School’s Derrick J. Rossi reported that it had developed a new way to reprogram adult stem cells into induced pluripotent stem cells, an embryonic stem cell-like state with the potential to be converted to many types of cells and tissues (Cell Stem Cell publication). And the researchers behind the technique have spun out a new startup, ModeRNA Therapeutics, to commercialize it, with backing from Flagship VentureLabs (press release).

Most of the techniques for generating these blank-slate cells permanently alter the cell genome. (The perhaps most well-known technique uses a virus to integrate additional genes into cells’ chromosomes.) In contrast, Rossi’s method uses synthetically modified messenger RNA molecules for reprogramming. The synthetic RNA’s don’t integrate into the cells’ genetic material.

ModeRNA’s founding team includes Rossi, Kenneth Chien, who leads the Massachusetts General Hospital Cardiovascular Research Center, and MIT biochemist Robert Langer, Xconomy reports.

Across the continent at Fate Therapeutics, researchers are also hard at work on reprogramming adult cells. Today they announced a deal with Becton Dickinson to jointly develop and commercialize its own induced pluripotent stem cell technology (press release). One of Fate’s scientific founders is chemist Sheng Ding, who is a leader in finding small molecules to manipulate cells and understand stem cell biology. Here’s a cover story by C&EN’s Sarah Everts that puts Ding’s work into the wider context of the stem cell field.

The first government-approved clinical trial to test a therapy developed from human embryonic stem cells is now underway. Geron Corp. has begun testing an embryonic stem-cell treatment on an Atlanta patient with spinal cord injuries, according to the Associated Press.

Finally, a promising young Harvard Medical School stem-cell researcher has retracted a January 2010 2009 Nature paper which suggested that some unknown factor from the blood of young mice helped blood-forming stem cells in older mice act young once again. (hat tip to Retraction Watch).

UPDATE 3:34PM 10/14 Updated year of retracted paper.
UPDATE 4:06PM 10/14 Retraction Watch is reporting that the journal Blood has issued a ‘notice of concern’ (a potential harbinger of a retraction) for a 2008 paper by the same group that published the retracted Nature work.

Can M.I.A. make stem cells sexy?

We interrupt our regularly scheduled posting on such mundane topics as drug discovery deals and clinical trial results to bring you a word from Tufts professor Jonathan Garlick, who is awfully excited about stem cells.  And for good reason: as the head of cancer biology and tissue engineering at Tufts’ Dental School, he managed to coax human embryonic stem cells into a three-dimensional tissue last year. This song–really, more of a rap–appropriately set to the tune of M.I.A.’s infectious “Paper Planes,” seems to focus a bit more on the political issues behind stem cell research. Here’s some more on Garlick’s views on the stem cell research, but you might want to wait until after you’ve seen his video. Awesome? Or are science music videos overplayed?