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Published on: January 7, 2019
Telocytes and putative stem cells in ageing human heart
Laurentiu M Popescu1, Antoanela Curici, Enshi Wang
1Department of Cellular and Molecular Medicine, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; Division of Advanced Studies, 'Victor Babeş' National Institute of Pathology, Bucharest, Romania.
Insights
The aging human heart has more interstitial cells and fewer cardiomyocytes than previously thought. Cardiac stem cell numbers decline significantly with age, impacting heart regeneration.
Area of Science:
- Cardiovascular Biology
- Cardiac Histology
- Regenerative Medicine
Background:
- Traditional views underestimate non-cardiomyocyte cell populations in the mammalian heart.
- Accurate quantification of cardiac stem cells (CSCs) during human aging is lacking.
- Telocytes (TCs) are a recently described cell type with potential roles in cardiac tissue.
Purpose of the Study:
- To identify and quantify cell types in the aging human atrial myocardium.
- To re-evaluate the cellular composition of the heart concerning age.
- To investigate the distribution of telocytes and cardiac stem cells in relation to age.
Main Methods:
- Electron microscopy was employed for cell identification and enumeration.
- Morphometric analysis of human atrial appendages from newborns, children, and adults.
- Computer-assisted technology was used for quantitative analysis of cellular populations.
Main Results:
- The interstitial area increases with age, while cardiomyocyte proportion remains high (76-88%).
- Blood capillary density significantly increases in children and adults compared to newborns.
- Cardiac stem cell numbers decrease fivefold from newborns to adults, suggesting reduced regenerative capacity.
Conclusions:
- Cardiac fibroblasts are not the most prevalent interstitial cell type as commonly believed.
- Telocytes, though numerically small, form a supportive network for cardiac stem cells.
- The age-related decline in cardiac stem cells likely explains the heart's limited regeneration potential.
Abstract:
Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days-1 year), children (6-17 years) and adults (34-60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm(2) ) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52-62%; vascular smooth muscle cells and pericytes 22-28%, Schwann cells with nerve endings 6-7%, fibroblasts 3-10%, macrophages 1-8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).
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