Aim: 

Recently we have isolated a class of Multipotent Adult Stem Cells (MASCs) from human hearts, bone marrows and livers. This class of stem cells displayed, in vitro, pluripotent state specific transcription factor expression, telomerase activity, clonogenicity and wide multipotency. The purpose of the present study was to establish whether stem cells residing in human atria obtained from explanted failing hearts showed an accelerated form of senescence and displayed functional impairment, both in terms of differentiation and migration capacity.

Methods: 

In order to do so, we isolated, grew in vitro and compared MASCs isolated from human atria both of: explanted failing human hearts (n = 22) and transplanted donor hearts (n = 12). Cell lines were first tested for their surface immunophenotype and for the expression of pluripotent state specific transcription factors (Oct-4 and Nanog). Furthermore, telomerase activity, telomeric length, telomere dysfunction, and senescence-associated markers were assessed. In order to verify MASC differentiation potential, cells were cultured either in a myogenic medium, and tested for the expression of alpha-sarcomeric actin, smooth muscle actin and connexin 43, or in an endothelial medium, and tested for vonWillebrand Factor expression. Finally the ability of MASC to migrate along a chemotactic gradient was tested in a migration assay.

Results: 

MASCs obtained from failing human hearts possess significantly lower levels of telomerase activity, shorter telomeres, and higher levels of telomere induced dysfunction foci. Moreover, these cells express higher levels of senescence-associated markers (p21 and p16). Furthermore, pathological cell lines displayed a statistically significant lower fraction of cells expressing myocyte specific markers. Importantly, actin filaments resulted to be less organized and connexin-43 more diffuse on the surface, without an elective localization at the intercellular adhesion sites. Similarly, the fraction of cells expressing vWF, upon differentiation, was significantly higher in donor derived cells. Finally, the migratory ability of MASCs derived from failing hearts was depressed.

Conclusion: 

MASCs can be isolated and grown from atria of normal and pathological human hearts. Although these cells share many important stem cell features, they differ not only in terms of telomeric length and growth kinetics, but also in terms of differentiation and migration capacity suggesting that pathological processes can impair the functional properties of the resident cardiac stem cell reservoir.