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Blood cells coaxed back into stem cells

JOHNS HOPKINS (US) — Scientists now have an efficient, virus-free way to turn adult blood cells back into stem cells for possible use in place of cells derived from human embryos.

The work, described in the August 8 issue of the journal PLoS One, is “Chapter Two” in an ongoing search for a method to consistently convert adult blood cells into stem cells, says lead researcher Elias Zambidis, assistant professor of oncology and pediatrics at the Johns Hopkins University School of Medicine.

“Taking a cell from an adult and converting it all the way back to the way it was when that person was a 6-day-old embryo creates a completely new biology toward our understanding of how cells age and what happens when things go wrong, as in cancer development.”


Stem cells are in a primitive state from which they can develop into any other type of cell in the body, a property that potentially makes them highly useful for both research and treatment. The use of human embryos to derive stem cells has been controversial. Using cells from adults to make them would be far less so.

“Chapter One” of Zambidis’ research was described in PLoS One in the spring of 2011. He and colleagues recounted then how they safely transformed adult blood cells into heart cells.

In the new report, they describe methods used in their latest experiments to turn back the clock on the blood cells, coaxing them to become “induced-pluripotent stem cells,” or iPS cells, adult cells reprogrammed to an embryonic-like state.

Zambidis says his team’s “super efficient” method overcomes a persistent difficulty for scientists working with these cells in the laboratory.  Generally, out of hundreds of blood cells, only one or two might turn into iPS cells. Using the new method, 50 to 60 percent of blood cells were engineered into iPS cells.

The team also found a way around the use of viruses in the conversion process. Scientists usually use viruses to deliver genes that turn on the processes converting cells back to the stem cell state.

Viruses used in this way can, however, mutate genes and initiate cancers in newly transformed cells. To insert the genes without using a virus, the Zambidis team is using plasmids, rings of DNA that replicate briefly inside cells and then degrade. In an additional new step, the blood cells also were stimulated in their natural bone-marrow environment.

The Johns Hopkins team took cord blood cells and treated them with growth factors. They then delivered an electrical pulse to the cells, making tiny holes in the surface through which the plasmids and genes could slip inside.

Once inside, the gene-carrying plasmids triggered the cells to revert to a more primitive cell state. The scientific team next grew some of the treated cells in a dish alone and some together with irradiated bone-marrow cells.

When scientists compared the cells grown using the blood cell method with iPS cells grown from hair cells and from skin cells, they found that the most superior iPS cells came from blood stem cells treated with just four genes and cultured with the bone marrow cells.

These cells converted to a primitive stem cell state within seven to 14 days. Their techniques also were successful in experiments with blood cells from adult bone marrow and from circulating blood.

In ongoing studies, Zambidis and colleagues are testing the quality of the newly formed iPS cells and their ability to convert to other cell types, as compared with iPS cells made by other methods.

Efficient methods to produce virus-free iPS cells may speed research to develop stem cell therapies, using nearly all cell types, and may provide a more accurate picture of cell development and biology.

Source: Johns Hopkins University

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