World Congress of Cardiology Report - Despite the dramatic advances in the care of patients with cardiovascular diseases that have occurred in the second half of the 20th century, heart failure (HF) is the most common cause of death in developed nations.
Moreover, HF prevalence is rising rapidly in the developing nations as well. It has been projected that by 2020 cardiovascular disease will be, for the first time in human history, the most common cause of death worldwide. At this time heart transplantation is the only therapeutical option for patients in the end stage heart failure, but a shortage of donors is a major problem.
New hopes came from the recent demonstration that mammalian hearts possess a stem cell reservoir constituted of primitive cells that contribute to the formation of new vessels and myocytes during the entire organism lifespan. “The heart can heal itself,” claimed the scientists, commenting that this ground-breaking discovery supports the possibility that, in case of heart damage, it may be possible to induce the stem cells residing in the heart to migrate to the sites of damage forming new vessels and myocytes.
The possibility to exploit this intrinsic “healing” source led our work.
We have first demonstrated in humans that, as in the animal model, failing hearts still possess cells that show all the features of stem cells in vitro. Cardiac stem cells (CSC) are indeed able to proliferate giving rise to other stem cells (property named self-renewal); they can differentiate into all the cells composing the cardiac tissue, for example myocytes and endothelial cells, (property named multipotency). Additionally, when seeded as single cells, they can proliferate, maintaining self-renewal and multipotency (property named clonogenicity). We have then established that atria are the heart region with the highest frequency in CSC, supporting the therapeutic strategies implying the mobilization or the isolation of the CSC from this reservoir.
However, several in vivo studies have suggested that the same pathological processes impairing the cardiac tissue can affect human CSC.
Therefore, the purpose of our study was to verify whether the CSCs that we recently identified as resident in the human heart change their properties in pathological states. For this reason, we isolated CSCs from atria of patients suffering from ischemic heart failure and undergoing transplantation (Recipient Heart, RH) and from atria obtained from donor hearts (Donor Heart, DH), which usually are not transplanted.
Qualitatively, RH and DH cells shared similar stem cell properties: they displayed a mesenchymal immunophenotype; they expressed OCT-4 and Nanog, proteins considered to be transcription factors expressed by embryonic stem cells and other stem cells characterized by multipotency; they possessed telomerase activity, a key feature in the attenuation of cell ageing consequent to extensive cell proliferation; they were clonogenic and multipotent.
Although RH- and DH- derived cell lines possessed telomerase activity, the average telomeric length, as evaluated by FLOW-FISH, was significantly lower in RH. Since telomeric shortening is considered to be of critical importance in human cell senescence, biologically RH cells seemed to age faster than DH cells.
Cells with a wide differentiation potential can be isolated and grown from atria of dhs and rhs. Although these cells share important SC features (immunophenotype, multipotency, clonogenicity, telomerase activity), they differ in terms of telomeric length and growth kinetics, suggesting that pathological processes can impair the resident cardiac SC reservoir. Because of the fact that the effect of telomerase and telomere length on stem cell behavior are intrinsic to the stem cell and do not depend on physiological niche micro-environments, the telomeric shortening of resident stem cells may represent an independent factor of the multifactorial heart failure patho-physiology.
Revision date: July 5, 2011
Last revised: by Sebastian Scheller, MD, ScD