The Heart is a Strange Sort of Organ

All organs are of course very different from one another, but some are more unusual than others. The heart is largely muscle, but muscle with strange characteristics, one of which is that it does an exceptionally poor job of regeneration following injury. This isn't what you'd like to hear regarding the second most vital organ in the body. As is also the case for the brain, it was only comparatively recently established that the adult heart generates any meaningful number of new replacement muscle cells over time. That flow of replacements is small enough and slow enough that even in old age it is still the case that most of your heart muscle cells were originally created in early childhood. The important thing for researchers in the field of regenerative medicine is that this flow exists at all, however. Given a natural process there will be ways to expand upon it, but this is still very young research even in comparison to similar investigations of ways and means to expand the trickle of neurogenesis in the adult brain.

Current first generation efforts to spur heart regeneration through stem cell therapies skip over all of these subtleties in a brute-force attempt to heal, but regenerative medicine is a field in which the numerous differences between organs matter greatly. Research groups tend to specialize on just a few tissue types at a time, hammering out protocols and knowledge needed to induce regeneration, none of which have immediate application to healing in other tissues. It is similar to the situation in cancer research, in which every cancer is radically different in the ways that matter, but with less of a hope of finding common points of action that should work in many different tissue types. Building tissue is always going to be harder than destroying tissue, and there will be far fewer shortcuts: it is the nature of things. Thus the development of regenerative medicine that builds upon, and eventually goes beyond, stem cell research will be a large and costly field of many specialties for decades. It heralded the start of the era in which degenerative aging will be effectively treated, and I imagine it will still be going strong and with much to accomplish well after the first suite of SENS-like rejuvenation treatments are commercialized.

Back to the heart, here are a couple of recent papers that look at the unusual dynamics of heart cells, particularly in heart muscle tissue:

Most heart muscle cells formed during childhood

New human heart muscle cells can be formed, but this mainly happens during the first ten years of life, according to a new study. Other cell types, however, are replaced more quickly. During a heart attack, when parts of the heart muscle are starved of oxygen, many heart cells die and are replaced by scar tissue. As this impairs functionality, many researchers are interested in the possibility of stimulating the regeneration of lost heart muscle cells. But is it possible?

To examine the regeneration of human heart cells, the team behind this new study used a combination of methods. One such was to measure the radioactive isotope C-14, exploiting the sharp rise in atmospheric levels of carbon-14 in the 1950s and 60s caused by nuclear testing. Levels then declined, which means that cells that were formed after that period give lower C-14 readings than those formed during it. Thus by measuring the amount of C-14 in a cell's DNA, the researchers were able to calculate its age. "We examined the heart tissue from 29 deceased individuals of various ages and found that even by one month after birth, the heart contains the same number of cells as it has in adults."

According to the study, the heart grows during childhood because its cells increase in size rather than in number; in other words, heart cells are generated on only a modest scale, and even during a long life, only forty per cent of muscle cells are replaced. "Our findings suggest that it can be rational and realistic to develop new therapeutic strategies for strengthening the body's own regenerative capacity to treat heart diseases."

Telocytes and putative stem cells in ageing human heart

Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes. The presence of telocytes has been overlooked, since they were described in 2010. Also, the number of cardiac stem cells has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium. Three age-related groups were studied: newborns (17 days - 1 year), children (6-17 years) and adults (34-60 years).

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 mm2) increased with several hundreds in children and adults versus newborns. Cardiomyocytes are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Interestingly, no lipofuscin granules were found in cardiomyocytes 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%, telocytes 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, telocytes represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports cardiac stem cells. The myocardial (very) low capability to regenerate may be explained by the number of cardiac stem cells, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).


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