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Shushing T cells promotes acceptance of stem cell therapies, say Stanford researchers

Embryonic stem cells are full of promise. But they're also peppered with red flags for the body's immune system, which recognizes them as foreign tissue and tries to destroy them. Unless the body can be coaxed to accept the cells it will be difficult to use them as therapy.

Now Stanford cardiologist Joseph Wu, MD, PhD, along with medical student Julia Ransohoff and postdoctoral scholar Bruno Huber, PhD, have outlined a novel new therapy to block the body's attack on the cells. The research was recently published (subscription required) in Stem Cells.

As Wu, director of the Stanford Cardiovascular Institute, explained to me in an e-mail:

Regenerative therapies hold great clinical promise, particularly for patients with damaged hearts and end-stage heart failure. But, surprisingly, promoting long-term stem cell graft acceptance is a much more formidable task than is supporting host acceptance of a vascularized solid organ such as a heart.

The researchers found that a course of treatment with two antibodies that block a pathway necessary for optimal T cell activation helps a laboratory mouse accept transplanted human stem cells. This new, dual-agent approach was more effective than a combination of prednisone and cyclosporin A - two more-broadly acting drugs that are currently used to suppress the immune systems of patients who have received organ transplants. Promoting the acceptance and engraftment of the human stem cells in a mouse model of myocardial infarction, or heart attack, also improved the animals' heart function, the researchers found.

But there's another important potential advantage. As Ransohoff explains:

In marked contrast to the life-long immunosuppressive regimens that transplant patients face, which leave them immunocompromised and susceptible to infection, our regimen is not only significantly more effective, but also requires only minimal dosage limited to the first week following transplantation.

Superior acceptance of stem cells with a single, short-course of treatment? Yes, please. There's still much work to be done to determine whether this approach would work in human patients. But it's tantalizing to imagine we're marching ever closer to a future in which therapies derived from human embryonic stem cells are routinely used to help people with heart problems.

Previously: Overcoming immune response to stem cells essential for therapies, say Stanford researchers and New technique prevents immune-system rejection of embryonic stem cells

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