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The atrioventricular junction - a potential niche region for progenitor cells in the adult human heart.
Stem Cells Dev. 2019 May 31;:
Authors: Vukusic K, Sandstedt M, Jonsson M, Jansson M, Oldfors A, Jeppson A, Dellgren G, Lindahl A, Sandstedt J
Abstract
A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined BrdU 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. Here, we aim to investigate whether a similar niche exist 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 boarder in the AVj co-staining 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. Together 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 here 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.
A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined BrdU 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. Here, we aim to investigate whether a similar niche exist 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 boarder in the AVj co-staining 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. Together 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 here 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.
PMID: 31146637 [PubMed - as supplied by publisher]
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