BioWorld International Correspondent

LONDON - A protein already under development as a therapeutic agent in myocardial infarction is capable of inducing immature cells found in the outer layer of the heart to migrate deeper and form new blood vessels.

An Anglo-American team of researchers has demonstrated that the protein, thymosin beta-4, plays a vital role in the development of cardiac blood vessels.

The research, published in the Nov. 15, 2006, issue of Nature, showed for the first time that immature cells capable of repairing the heart are present in the heart itself. Before the study, scientists thought that such cells, if they existed at all, were present only in the bone marrow.

Paul Riley, senior lecturer at the UCL Institute of Child Health in London, told BioWorld International: "Before this study, we had no idea that there were cells in the adult heart that could be triggered to develop in this way. Our findings suggest that, in the future, thymosin beta-4 could be used not only to treat people who have had heart attacks, but also to improve blood supply in the heart in people with blocked cardiac arteries."

Regenerx Pharmaceuticals Inc., of Bethesda, Md., is planning clinical trials of thymosin beta-4 as a treatment following myocardial infarction.

Riley and his colleagues, together with collaborators in the U.S., reported their study in a paper titled "Thymosin beta-4 induces adult epicardial progenitor mobilization and neovascularization." The first author is Nicola Smart.

The group's main interest is the factors affecting the development of the heart in the human embryo. Studies in mice had shown that a protein encoded by a gene called Hand1 influences the early formation of the heart. In a screen for genes that act downstream of Hand1, the Riley group first identified thymosin beta-4 as coming into play during heart development.

Thymosin beta-4 is known to regulate the actin cytoskeleton in most mammalian cells, with an important role in the regeneration, remodelling and healing of injured or damaged tissues. Riley set out to discover what its role was in the developing heart.

The team studied mice that had been genetically modified so that their heart muscle lacked thymosin beta-4. The researchers found that the hearts of those mice did not develop normally. The heart muscle showed early signs of tissue breakdown, and the development of the blood vessels in the animals' hearts was poor.

Further investigations showed that the cells affected by the lack of thymosin beta-4 were those in the epicardium, which had failed to move into the muscle layer of the heart. Instead, those progenitor cells stayed where they were.

The finding begged the question of how the heart from an adult mouse would respond to thymosin beta-4. So the researchers took tissue from the outermost layer of adult mouse hearts, grew it in the laboratory and added thymosin beta-4. Riley said: "We got an amazing response - the cells started to move away from the tissue, and experiments showed that these cells were forming the specialist cells needed to form blood vessels. But without thymosin beta-4, there was no cell movement and no cells capable of forming blood vessels."

Current treatments for a damaged heart are limited by the ability of the adult tissue to respond. Riley speculated that it may be possible in the future to use thymosin beta-4 to guide progenitor cells from the outer layer of the heart to new positions where they could form blood vessels that would nourish regenerating tissue.

That strategy could improve on existing and experimental treatments aimed at repairing the damage caused by myocardial infarction.

Riley added: "In the future, there could be the potential for therapy based on the patients' own heart cells. This approach would bypass the risk of immune system rejection, a major problem with the use of stem cell transplants from another source. And it has the added benefit that the cells are already located in the right place - within the heart itself. All these cells need are the appropriate instructions to guide them toward new blood vessel formation that will help in the repair of muscle damage following a heart attack."