Medical Q&A: Progress made in getting stem cells to ‘take’ in mice – Sarasota Herald-Tribune

By Sykes24Tracey

Q: How close are we to curing blood diseases with human stem cells?

A: New research has nudged scientists closer to one of regenerative medicine's holy grails: the ability to create customized human stem cells capable of forming blood that would be safe for patients.

Advances reported in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukemia, lymphoma and myeloma. They could also improve the treatment of those cancers, which affect some 1.2 million Americans.

While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment.

The blood-making stem cells that reside in a donor's bone marrow and in umbilical cord blood harvested after a baby's birth are called "hematopoietic," and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. So they can provoke an attack if the transplant recipient's body registers the cells as foreign.

This response, called graft-versus-host disease, affects as many as 70 percent of bone-marrow transplant recipients soon after treatment, and 40 percent develop a chronic version of the affliction later. It kills many patients.

Rather than hunt for a donor who's a perfect match, doctors would like to use a patient's own cells to engineer the hematopoietic stem cells.

The patient's mature cells would be "reprogrammed" to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become stem cells capable of giving rise to blood.Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells.

If the risk of rejection could be eliminated, physicians might also feel more confident treating blood diseases that are not immediately deadly such as sickle cell disease and immunological disorders with stem cell transplants.

One of two research teams, led by stem cell pioneer Dr. George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute, started their experiment with human "pluripotent" stem cells primitive cells capable of becoming virtually any type of mature cell.

The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels.Using suppositions gleaned from experiments with mice, Daley said his team confected a "special sauce" of proteins that sit on a cell's DNA and program its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells.

Daley's team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would "take." In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells.

A second team, led by researchers from Weill Cornell Medicine's Ansary Stem Cell Institute, achieved a similar result using stem cells from the blood-vessel lining of adult mice.

But Daley cautioned that significant hurdles remain before studies like these will transform the treatment of blood diseases.

"We do know the resulting cells function like blood stem cells, but they still are at some distance, molecularly, from native stem cells," he said.

Melissa Healy, Los Angeles Times

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Medical Q&A: Progress made in getting stem cells to 'take' in mice - Sarasota Herald-Tribune

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