Calcium is crucial for heart regeneration by cardiac stem cells following cardiovascular problems say scientists in an article to be published in the journal Circulation Research this 9th of October. The study also identifies the body molecules controlling calcium levels in the stem cells and reveals, how their manipulation, can lead to the formation of new cardiac tissue. The work, that follows the recent surprising discovery of stem cells within the heart, can have important implications in the regenerative medicine of this organ in patients with cardiovascular diseases.
Heart injuries are extremely difficult to treat; the lack of blood flood following injury or during disease kills heart muscle cells and results - because the healing scar tissue does not function as the original muscle - in loss of function, which, depending on the extension of the injury, might lead to heart failure. The only alternative is heart regeneration through the production new cardiac muscle cells (cardiomyocytes) that replace the dead tissue. Unfortunately, cardiomyocytes once differentiated, scarcely divide again. The most promising alternative source of new cells are cardiac stem cells, but these - although found around the diseased tissue following a heart attack - appear to have very limited regenerative capability when disease occurs.
Trying to understand better the mechanisms and molecules behind these stem cells, in an attempt to improve their regenerative capabilities, led Joao Ferreira-Martins, Carlos Rondon-Clavo and colleagues at Harvard Medical School and the University of Milano-Bicocca in Milan to study their calcium levels. In fact, not only calcium levels have been specifically linked to the mechanical behaviour of cardiomyocytes, but they are also known to affect several physiological processes such as cell division, development and differentiation.
By using a calcium-sensitive fluorescent dye that could be measured the researchers were able to discover that human cardiac stem cells show spontaneous oscillations in their internal calcium levels, with the higher values being found right before cell division. They also identified three naturally occurring molecules regulating these oscillations: ATP, Histamine and insulin-like growth factor 1 (IGF-1). Interestingly, when cardiac stem cells grew in the presence of any of these molecules there was a substantial increase in cells showing oscillating calcium levels as well as in the frequency of these oscillations, and also in the numbers of cells dividing, all characteristics of what appears to be an "activated state".