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Rewriting Life

Stem Cells Made with RNA

A new technique could provide safer cells for human therapies

Source: “Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA”
Derrick J. Rossi et al.
Cell Stem Cell 7(5): 618-630

Rebirth: Stem cells reprogrammed with RNA can develop into different cell types.

Results: Researchers used four types of RNA molecules to “reprogram” adult cells so that they behaved like embryonic stem cells, which are capable of turning into any cell type. Then they used them to create muscle cells. The new method is 100 times as efficient as conventional cell reprogramming methods, which use DNA rather than RNA.

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Why it matters: Scientists would like to be able to create personalized replacement tissue by turning a patient’s own cells into stem cells and then coaxing those cells to differentiate into the type of tissue that has been lost or damaged by disease. The most common reprogramming technique involves inserting four genes into an adult cell. But this type of genetic engineering might increase cancer risk, so the resulting cells cannot be used in human therapies. The new method is one of several DNA-free approaches now under development.

Methods: The researchers created synthetic RNA molecules, adding chemical modifications that enabled the molecules to escape immune attack when introduced into a cell.

Next steps: Additional molecular testing must confirm that the cells created from these reprogrammed cells closely resemble normal adult versions. Derrick Rossi, the Harvard researcher who developed the technology, has started a company to commercialize it.

Stroke Therapy

A drug that blocks inhibitory nerve signals improves recovery

Source: “Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke”
S. Thomas Carmichael et al.
Nature 468(7321): 305-309

Results: Researchers found that after a stroke, neurons near the damaged part of the brain are blocked from firing, which makes it more difficult for the brain to incorporate them into new circuits that might compensate for the damage. The problem stems from the buildup of a molecule that inhibits the neurons’ signaling functions. By treating stroke-damaged mice with an existing compound three days after inducing the stroke, the researchers were able to block the effects of this buildup. The treatment boosted recovery of motor function by 30 to 50 percent.

Why it matters: The brain has some ability to “rewire” itself after a stroke, in which a blood clot blocks blood flow to a part of the brain and deprives it of oxygen. Even with intensive rehabilitative therapy, however, most patients never fully recover lost movement or language skills. Existing drugs for stroke prevent the blood clot from doing additional damage, but they do not enhance the brain’s ability to rewire. In addition, the drugs must be taken within a few hours of the stroke, and not all victims can get help in time.

Methods: After inducing a stroke in mice, researchers found that a transporter molecule normally responsible for removing the inhibitory chemical from brain tissue was no longer functioning properly. But giving the mice an experimental drug known to suppress the action of this chemical improved their motor function.

Next steps: The researchers now plan to test whether the same treatment works for different types of strokes in different parts of the brain. The experimental drug used in the study is not approved for human use, so the team wants to work with pharmaceutical companies to encourage clinical testing of this compound or others that have a similar effect.

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