The Atrioventricular Junction: A Potential Niche Region for Progenitor Cells in the Adult Human Heart.
A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined 5-bromo-2-deoxy-uridine labeling with activation of endogenous stem cells by physical exercise and revealed a distinct region, in the atrioventricular junction (AVj), with features of a stem cell niche. In this study, we aim to investigate whether a similar niche exists in the human heart. Paired biopsies from AVj and left ventricle (LV) were collected both from explanted hearts of organ donors, not used for transplantation (N = 7) and from severely failing hearts from patients undergoing heart transplantation (N = 7). Using antibodies, we investigated the expression of stem cell, hypoxia, proliferation and migration biomarkers. In the collagen-dense region of the AVj in donor hearts, progenitor markers, MDR1, SSEA4, ISL1, WT1, and hypoxia marker, HIF1-α, were clearly detected. The expression gradually decreased with distance from the valve. At the myocardium border in the AVj costaining of the proliferation marker Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin-T (cTnT) indicated proliferation of small cardiomyocytes. In the same site we also detected ISL1+/WT1+/cTnT cells. In addition, heterogeneity in cardiomyocyte sizes was noted. Altogether, these findings indicate different developmental stages of cardiomyocytes below the region dense in stem cell marker expression. In patients suffering from heart failure the AVj region showed signs of impairment generally displaying much weaker or no expression of progenitor markers. We describe an anatomic structure in the human hearts, with features of a progenitor niche that coincided with the same region previously identified in rats with densely packed cells expressing progenitor and hypoxia markers. The data provided in this study indicate that the adult heart contains progenitor cells and that AVj might be a specific niche region from which the progenitors migrate at the time of regeneration.
['Vukusic|Kristina|K|', 'Sandstedt|Mikael|M|', 'Jonsson|Marianne|M|', 'Jansson|Märta|M|', 'Oldfors|Anders|A|', 'Jeppsson|Anders|A|', 'Dellgren|Göran|G|', 'Lindahl|Anders|A|', 'Sandstedt|Joakim|J|']
D000328:Adult D000368:Aged D015415:Biomarkers D002454:Cell Differentiation D049109:Cell Proliferation D005260:Female D006333:Heart Failure D016027:Heart Transplantation D006352:Heart Ventricles D006801:Humans D008297:Male D008875:Middle Aged D009206:Myocardium D032383:Myocytes, Cardiac D055153:Stem Cell Niche D013234:Stem Cells D014019:Tissue Donors D055815:Young Adult
atrioventricular junction heart stem cell niche hypoxia cardiomyocyte proliferation