Science news from Harvard Stem Cell Institute

Public release date: 29-May-2013 [ | E-mail | Share ]

Contact: Joseph N. Caputo 617-476-1492 Harvard University

May brought a major advancement in the science of aging when two Harvard Stem Cell Institute (HSCI) researchers announced their discovery of a protein circulating in the blood of mice and humans that shows potential to be a treatment for age-related heart failure. The protein, called GDF-11, reduced the size and thickness of the heart walls when injected into old mice.

There are hundreds of investigators in the HSCI network solving different problems related to cell biology and illness. This month, we feature recently published work by three laboratories on: a therapy for graft-versus-host disease, intestinal stem cell circadian rhythms, and new hope for people suffering from a rare blood disorder.

Human Clinical Trials Move Forward With Promising Therapy for Graft-Verses-Host Disease

HSCI investigators have developed a better picture of why a recently discovered therapy for graft-versus-host disease (GVHD) is more effective than anything currently available to patients.

In 2011, human clinical trials showed that immune system signaling molecule interleukin 2 (IL-2) both improved GVHD symptoms in patients and completely stopped the progression of the condition. Surprisingly, HSCI Executive Committee member Jerome Ritz, MD, and his team at the Dana-Farber Cancer Institute found that patients who received a continuous low dose of IL-2, which is an FDA-approved drug that stimulates immune cells to attack certain types of cancers, saw reduced GVHD symptoms because their immune response was suppressed. "It's interesting because it changes the paradigm," Ritz said. "You think something stimulates the immune system, but actually what it does is the opposite."

Bone marrow transplants are life-saving treatments for patients with leukemia and lymphoma that completely replace a recipient's faulty blood-forming stem cells with those of a matching donor. Despite immunologic differences between the donor and recipient, the donor immune system often recognizes that it is in a new place and adapts. When recognition does not happen, the donor's immune system begins to attack the recipient's tissues, causing the uncomfortable and difficult-to-manage symptoms of GVHD.

Ritz's team found that IL-2 affects the relationship between the immune cells that mount the body's immune response (effector T cells) and the immune cells that maintain the body's ability to differentiate between self and non-self tissue (regulatory T cells). The researchers observed that patients with GVHD have a lower level of regulatory T cells and higher level of effector T cells than normal. Low doses of IL-2 can increase the presence of regulatory T cells sevenfold and help them survive longer. The growing population of regulatory T cells then competes for IL-2 with effector T cells, preventing them from getting switched on.

"The immune system functions in checks and balances," Ritz said. "We found that not only was their relatively less IL-2 in GVHD patients, but there was relative more other cytokines, IL-7 and IL-15, that primarily supported effector T cells and didn't support regulatory T cells." Ritz's work is inspiring multi-center studies looking at how IL-2 can work in other immune diseases, and whether early use of IL-2 can reduce tissue damage caused by GVHD.

Science news from Harvard Stem Cell Institute

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