"Studies on the cardiomyocytic potential of dermal stem cells”

Abstract

In Europe, diseases of the heart and circulatory system are the main cause of death; 48% of all deaths are from coronary heart disease, accounting for over 4.30 million deaths each year (European cardiovascular disease statistics 2008). Identifying stem cell types that can potentially contribute to the regeneration of cardiac tissue is one route to addressing this global problem. The follicular dermis has been proposed as a tissue containing cells with adult stem cell properties that could be used for regenerative medicine. This study showed that follicular dermal structures demonstrated spontaneous synchronised contractions in vitro, indicative of cardiomyocytic commitment. In contrast, isolated populations of follicular dermis, the dermal papilla and sheath, did not demonstrate spontaneous cardiomyocytic commitment in vitro. Co-culture of isolated follicular dermal populations with embryonic cardiomyocytes, a cell type previously reported to support cardiomyocytic commitment of mesenchymal stem cell types, induced expression of a panel of gene products indicative of cardiomyocytic commitment, but only when the inducing cell and the target cell were of the same species. The level of gene induction indicated that the number of cells affected were likely to be very modest. In order to better identify the stem cell types in the follicular dermis, this study used a novel mTert-GFP transgenic mouse to identify candidate stem cells on the basis of their expression of the stem cell phenotypic marker, telomerase. A small population of GFP-expressing non-haematopoietic cells present in the dermis (0.17- 0.49%) were identified and found associated with the follicular dermis and bulge region. This minor sub-population of GFP-expressing dermal cells contained all the detectable gene expression of four key markers of stem cells: Tert; Oct4; Nanog and Sox2, both at time of isolation and after 2 weeks in vitro culture. Intriguingly, non- haematopoietic, GFP-expressing cells were also detectable in the adult heart at low level (0.08%). After cryo-induced infarct, these non-haematopoietic GFP-expressing cells were associated with the epicardium, concentrated close to the infarct site, in a fashion consistent with other reports of candidate cardiac stem cells. This study indicates that the population of stem cells within the follicular dermis may be very modest. Further, it shows that phenotypic markers of stem cells from different organs may be a suitable approach for the investigation of the stem cell phenotype.