Stem cell experiment reverses aging in rare disease

In a surprise result that can help in the understanding of both aging and cancer, researchers working with an engineered type of stem cell said they reversed the aging process in a rare genetic disease.

The team at Children's Hospital Boston and the Harvard Stem Cell Institute were working with a new type of cell called induced pluripotent stem cells or iPS cells, which closely resemble embryonic stem cells but are made from ordinary skin cells.

In this case, they wanted to study a rare, inherited premature aging disorder called dyskeratosis congenita. The blood marrow disorder resembles the better-known aging disease progeria and causes premature graying, warped fingernails and other symptoms as well as a high risk of cancer.

It is very rare and normally diagnosed between the ages of 10 and 30. About half of patients have bone marrow failure, which means their bone marrow stops making blood and immune cells properly.

One of the benefits of stem cells and iPS cells is that researchers can make them from a person with a disease and study that disease in the lab. Harvard's Dr. George Daley and colleagues were making iPS cells from dyskeratosis congenita patients to do this.

But, reporting in Thursday's issue of the journal Nature, they said the process of making the iPS cells appeared to reverse one of the key symptoms of the disease in the cells.

In this disease, the cells lose telomerase, an enzyme that helps maintain the telomeres. These are the little caps on the ends of the chromosomes that carry the DNA.

When telomeres unwind, a cell ages. This leads to disease and death.

BECOMING IMMORTAL

But in cancer, telomerase appears to help tumor cells become immortal and replicate out of control. Some experimental cancer drugs target telomerase.

A gene called TERC helps restore the telomeres and Daley's team said it may be that tumor cells make use of TERC to become immortal.

In making the iPS cells and getting them to grow in the lab, Daley's team discovered they had three times as much TERC as the diseased cells they were made from.

Simply turning the skin cells into iPS cells helped restore their damaged telomeres, Daley's team reported. This in theory stops a major component of the aging process as well.

“We're not saying we've found the fountain of youth, but the process of creating iPS cells recapitulates some of the biology that our species uses to rejuvenate itself in each generation,” Daley's colleague Suneet Agarwal said in a statement.

Treatments that restore TERC may help dyskeratosis congenita patients, they said.

“This paper illustrates how reprogramming a patient's skin cells into stem cells can teach us surprising lessons about human disease,” Daley added in a statement.

Agarwal says the team is now seeking funding to study this more.

Patients with dyskeratosis congenita often die when they get bone marrow transplants, Agarwal said.

“For these patients, and for patients with other bone marrow failure syndromes, it would be ideal to give them a gentler stem cell transplant from their own cells,” he said.

http://www.reuters.com/article/idUSTRE61G4SC20100217