Stem cells in heart regeneration Understanding the process of cardiac regeneration is of fundamental importance for the design of regenerative therapies. Health © Thinkstock Many chronic cardiomyopathies and myocardial infarction lead to cardiac muscle death. If apoptotic cardiomyocytes do not get replaced this can lead to severe deficiencies in cardiac pump function. Recent evidence supports the existence of cardiac progenitors with a multi-lineage stem cell potential and likely involvement in the natural regenerative capacity of the heart. Previous work by the project consortium identified the presence of Sca1 and platelet-derived growth factor alpha as cellular markers associated with cardiac progenitors. To further delineate the mechanism behind heart regeneration, scientists on the EU-funded CARDIAC ABC'S (Role of the ATP-binding cassette transporter Abcg2 in cardiac regeneration) focused on the role of the chromosome ends known as telomeres. Following systematic evaluation of cardiac progenitors, researchers discovered that these cells exhibited improved clonogenic capacity when cultured in low-oxygen conditions, and they had significantly longer telomeres. To elucidate the role of telomeres, they used mice deficient in the telomerase reverse transcriptase (TERT), the enzyme that adds nucleotides at chromosome ends and hence maintains their length. As expected, subsequent generations of mice lacking TERT exhibited signs of premature ageing and infertility. Investigation of cardiac progenitors lacking this enzyme is instrumental to understanding how telomeres shape regeneration and affect DNA integrity in these cells. Taken together, the generated information could form the basis for designing treatment strategies after injury or for boosting tissue regenerative capacity that declines with ageing. Given the role of stem cells in many tissues, the results of the CARDIAC ABC'S project extend beyond cardiac progenitors. Keywords Stem cells, heart, cardiac regeneration, cardiac progenitors, telomeres, TERT
