New Research: Repairing the Heart with Thymosin-β4

The major cause of death in the developing world is cardiovascular disease. This is usually due to the heart's failure to meet the needs of the rest of the body, usually due to a heart attack or due to defects in heart structure. In a heart attack, coronary arteries are blocked, preventing the heart from receiving oxygen, which leads to tissue death and the associated pain. Unlike fish which can regenerate new muscle cells, humans cannot fully regenerate new heart muscle cells to replace the dead ones.

One aim of cardiac regenerative medicine is to repair the damage after a heart attack. Several strategies have been proposed. One includes taking embryonic stem cells and turning them into cardiac muscle cells; these would be grafted back into the damaged tissue to repair the heart. Another strategy is to try and inject stem cells directly into the heart from various organs. However, an ideal strategy would be a less invasive method that involves harnessing the body's own stem cells and turn them into heart cells within the patient.

The heart is surrounded by a layer called the epicardium (epi for around, cardium for heart). The epicardium plays a crucial role in heart development. Firstly, it sends instructions to the heart to program its development. In addition, the epicardium is a source of heart progenitor stem cells, which move into the heart and mature into heart muscle cells during development. One characteristic of these cells is that they have the gene Wt1 turned on. However up to now, none of these cells appeared to be detected in adults.

A recent paper by Nicola Smart from Paul Riley's group found an important breakthrough in understanding this process. For the first time, they detected cardiac progenitors within the heart. The secret was to add a a special molecule called thymosin-β4 (Tβ4), previously reported to enhance repair of the blood vessels in the heart after heart attacks. Upon addition of Tβ4 to epicardium biopsies, they could detect the presence of progenitors as well as functional heart muscle cells.

Interestingly, she was also able to detect progenitors with the Wt1 gene turned on in adults after a heart attack. They appeared about 7 days after a heart attack, and are linked with the limited cardiac regeneration seen after a heart attack. The stunning thing was an injection of Tβ4 before a heart attack caused the progenitors to appear earlier (2 days later) and at larger numbers. Not only that, these progenitors could turn into functional heart muscle cells that integrated into the damaged heart tissue. Also, the heart with Tβ4 pre-treatment worked better after a heart attack than the heart which had not received any treatment.

What does this mean? Firstly, we now know that there are cells with stem cell capabilities in the heart. Secondly, the addition of Tβ4 can enhance the regeneration abilities of the heart upon suffering a heart attack. While the study only looked at pre-treating hearts with Tβ4, it will be interesting to see if the results translate to patients who receive Tβ4 right after a heart attack. If this ends up holding true, one can see a potential therapeutic use for heart regeneration after heart attacks.


Smart, N. et al. (2011). De novo cardiomyocytes from within the activated adult heart after injury. Nature 474, 640-44. Paper