Hsueh MF et al. Analysis of “old” proteins unmasks dynamic gradient of cartilage turnover in human limbs. Science Advances, October 2019.

Humans may not be able to regrow amputated limbs, but a recent study showed that damaged cartilage may regrow through a process similar to that of animals such as salamanders and zebrafish. Scientists collected 18 specimens of joint tissue from the hips, knees, or ankles of patients who underwent surgery. They then placed the tissue in a mass spectrometer and measured the age of the cartilage proteins in the sample. These analyses showed that the age of cartilage largely depended on where it resided in the body. Cartilage in ankles is young, middle-aged in the knee, and old in the hips. This correlation between the age of human cartilage and its location in the body suggests that limb repair occurs in humans in a similar fashion to certain animals in which tissue regeneration takes place at the furthest tips such as the ends of legs or tails. This finding also helps to explain why injuries to people’s knees and, especially, hips take a long time to recover and often develop into arthritis, while ankle injuries heal quicker and less often become severely arthritic. The researchers further identified the molecules that are instrumental in the regulation of this region-specific regeneration process. They are called microRNAs and, not surprisingly, are present at very high levels in animals that are known for limb, fin, or tail repair including salamanders, zebrafish, and lizards. Scientists believe that these regulator microRNAs can be utilized in the regeneration of degenerated cartilage of an arthritic joint to reverse arthritis. Regeneration of part or all of an injured human limb may even be possible by finding components salamanders have and we don’t. Finally, it is also possible that this could be a fundamental mechanism of repair that could be applied to many tissues, not just cartilage, which might open up many new avenues in the regenerative medicine.

The universe might have many Earth-like exoplanets

Doyle AE et al. Oxygen fugacities of extrasolar rocks: Evidence for an Earth-like geochemistry of exoplanets. Science, October 2019.

New astrophysical and geochemical evidence suggests that Earth may not be that unique, and Earth-like planets may be common in the universe. All of the planets in our solar system orbit around the Sun. Planets that orbit around other stars are called exoplanets.  The first exoplanets were discovered in the early 1990s. Since then, thousands of exoplanets have been revealed with over 4,000 confirmed and a further 4,495 potential candidates. There have been major efforts to narrow down the exoplanets that may have properties similar to Earth with conditions suitable for life. This includes being a rocky planet that is not too hot or cold so that liquid water can exist. When searching for exoplanets that are similar to Earth, astronomers typically look for worlds in orbit around a type of star called a red dwarf or an M-dwarf. These types of stars are somewhat similar to our sun and make up about 70% of the stars in our galaxy. However, a new study shows that rocky exoplanets in orbit around a different type of star, a white dwarf, can have interiors that are surprisingly similar to our planet. White dwarf stars are dense remains of normal stars that have exhausted their nuclear fuel. These stars are typically composed of light elements such as hydrogen and helium, but in some cases they attract heavier elements such as magnesium, iron, and oxygen in their atmospheres due to their extreme gravity. These heavy elements are thought to be introduced when a rocky exoplanet crashes into a star, which gives astronomers evidence of what the exoplanets were like before they were destroyed. In this recent study, scientists looked at six white dwarfs located 200 to 665 light-years from Earth and rocks from the planets that once orbited it. Their analyses showed that five out of the six white dwarfs had sucked up fragments whose chemical composition is similar to rocks on Earth, Venus, and Mars. While the conditions suitable for life depend upon many additional factors, this study points towards the idea that many rocky planets are likely very familiar in terms of their general composition and, therefore, structure and behavior. This study also made a substantial leap forward in being able to make inferences for bodies outside of our own solar system and indicates that it is very likely that there are truly Earth analogs out there.

Artificial leaf points to a sustainable path to carbon-neutral fuels

Andrei V et al. Bias-free solar syngas production by integrating a molecular cobalt catalyst with perovskite–BiVO4 tandems. Nature Materials, October 2019.

An artificial leaf from which a “clean” fuel alternative to petrol could be produced has been developed. Synthetic gas can be obtained from the lead by using only sunlight, carbon dioxide, and water.

Synthetic gas, also called syngas, is typically a mixture of carbon monoxide and hydrogen. It is largely produced by exposing fossil fuels such as coal or natural gas to high temperature steam and pressure, and the process releases carbon dioxide. Syngas is broadly used in a wide range of commodities including fuels, plastics, and fertilizers. While the utilization of fossil fuels has enabled large-scale industrial development in human history, the burning of fossil fuels is the largest source of emissions of carbon dioxide, which is one of the greenhouse gases that contributes to global warming. For decades scientists have been trying to discover new ways to produce syngas in order to close the global carbon cycle and to establish a sustainable chemical and fuel industry. In a recent study, researchers got inspired by leaves. These perfect little machines use sunlight to convert carbon dioxide and water into fuel for plants through photosynthesis. An artificial leaf has been designed to have two light absorbers, similar to the molecules in plants that harvest sunlight, and a catalyst made from the naturally abundant element cobalt. When the leaf is immersed in water, one light absorber uses the catalyst to produce oxygen and the other one carries out the chemical reaction that reduces carbon dioxide and water into carbon monoxide and hydrogen, thus forming the syngas mixture. The scientists are now searching for ways to use their technology to produce a sustainable liquid syngas that could serve as an alternative to petrol. Although major efforts to generate renewable energy sources are being made, the development of synthetic petrol is critical as electricity can currently fulfill about 25% of our total global energy demand. There is a huge demand for liquid fuels to power heavy transport, shipping, and aviation sustainably.

Nerve cells that fail to establish connections with other cells (nerve, muscle, or secretion gland) within the initial 6-12 month period following birth are destined for a programmed cell death (apoptosis). For example, if the eyes of newborn animals are kept shut for a couple of weeks, vision-related neurons in the brain cortex die and the animals become blind. If the initially present neurons cannot perform their duties or are not used properly, they are terminated. This situation is expressed as the “use it or lose it” principle.

The notion that there is no recuperation for injured or dead nerve cells or tissues, in addition to the recovery of bodily functions related to the damaged neural tissues, was dominant in the medical field for years. Even though this is the case for adult individuals, at least most of the time, it has been proven that this is not true and applicable all the time, especially for children. It has been discovered that lost brain functions can be recovered, even if only partially, and this potential for recuperation is present at birth. This is called the neuronal plasticity or regeneration (renewal) capacity.

Neuronal regeneration is the auto-healing process of nerve tissues that have lost their integrity, functions, or been damaged due to trauma, oxygen deprivation (ischemia), infection, or many other reasons. For example, in patients with polio, certain arm-leg nerve fibers become dead and the muscle stimulated by that nerve suffers a stroke. However, neighboring nerves manage to recover the paralyzed muscles by extending new arms. This situation may resemble the installation of a parallel phone line from your apartment to your neighbor when the old line is cut, which benefits both units with the same line. Certain short projections can grow from the root of a damaged or broken nerve fiber (axon), and in some cases healing may be achieved by this growth. According to the neuronal plasticity theory, the brain is a dynamic, flexible organ, and is open to changes. It is not static, and it can adapt to new conditions. Based on this theory, a brain that has lost an ability, such as vision or hearing, can regain these functions; an individual can hear or see again. However, there is still more research to be done on this matter.

Regeneration is a mechanism that supports the plasticity theory. The proliferation of stem cells is triggered by plasticity. The reassignment of the tasks of the dead nerve cells to other cells occurs; the surviving nerve cells are induced to develop new branches (dendrites or axons). With the discovery of the plasticity and regeneration processes, some diseases that have been considered untreatable have shown signs of being treatable. For instance, during cerebral palsy in children, imperfections take place regarding motor movements, perception, and intelligence, depending on the oxygen deprivation experienced in the brain tissue before, during, or after birth. The brain goes through an adaptive process to execute the missing functions. Especially during the early stages of life, it is understood that the brain cortex is created with extraordinary reorganization abilities after an injury.

Plasticity not only manifests itself via an increased neuron count, but also with an increase in the number of axons and dendrites, in addition to an abundance of synapses among nerve cells. Nonetheless, the onset of all the positive changes on the neurons requires a stimulator or a trigger. In recent years, certain drugs were developed for this purpose. The laboratory works showing that neuronal plasticity and regeneration were successful for polio also give hope that adult brain disorders might be treatable. Brain recuperation via neuronal plasticity is not only dependent on drugs, but also can be achieved by alternative methods like acupuncture, touching, and massage therapy. Apart from these, sports like swimming and horseback riding are known to stimulate and trigger regeneration in damaged neurons.

The studies briefly explained here have proven wrong the belief that the central nervous system cannot heal and recover to its normal mode of functioning. Mechanisms that have been established in the system (the genetic structure) are being newly discovered by mankind. New studies are needed to find out what other aspects of human biology can be discovered as the science advances. Such discoveries remind us of what a remarkable creation human beings are.

Heart regeneration in mammals

Such heart regeneration holds the promise for the treatment of heart failure following heart attacks. But so far, the adult human heart is known not to show adequate regeneration or replacement of dead tissue with functional tissue such as beating cardiomyocytes (cardiac muscles) and arteries. When a patient has successive heart attacks and myocardial infarctions (death of cardiac muscle resulting from interruption of the blood supply), the number of dead cells increases due to the decreased level of oxygen reaching the heart tissue. That’s one of the reasons heart disease is so deadly.

The rates of cardiac regeneration, from fish to amphibians to mammals, demonstrates a decreasing trend — high in fish, moderate in amphibians, and limited in mammals. The regeneration mechanism is thought to occur via incorporating stem cells, using differentiation into cardiac muscle and other cell types, or via dedifferentiation of cardiomyocytes. It is known that the heart of an adult zebra fish can regenerate without scar formation, whereas adult rodents and humans respond with a fibrous scar, without obvious cardiomyocyte regeneration. This remarkable phenomenon had been demonstrated in other fish and amphibians, but never before in a mammal. Recently, researchers at UT Southwestern Medical Center showed that a newborn mouse’s heart can fully heal itself.

Sadek’s group at UT Southwestern Medical Center at Dallas showed that the mammalian heart demonstrates a temporary regeneration capacity in newborn mice. After slowing down the body functions by cooling the body of a mouse, they performed a very delicate heart surgery, removing about 15 percent of the apex of a 1-day-old newborn mouse heart. Within a short period (three weeks), they showed that heart had healed and the function of heart had returned to normal. But when mice are a week old, this remarkable ability of regeneration disappears, and damage to the heart results in the thinning of the heart wall at the site of injury, and the loss of the pumping capacity of heart, also known as heart failure. There seems to be a barrier to regeneration after 7 days. This 7-day window in mice could correspond to a few months after birth in humans. Several reports suggest that human heart may also have some ability to regenerate in infancy.

If newborn animals and infants are able to regenerate their hearts, there could be ways to remind the heart how do this or restart this ability in adulthood to allow regeneration in a broader window. Could there be means to induce regeneration by gene therapy, using small molecules, drugs or hormones? This new discovery brings new approaches to study heart disease and hopes that one day, heart disease — the number one killer in the world — could be treated. More studies are needed and a number of labs have already started to invest in this new model of heart regeneration.

Human heart cell turnover and regeneration

The heart is the least regenerative organ in our body. Once cardiomyocytes are damaged through heart attacks, the heart heals by scar formation instead of regeneration. This results in a loss of contractile function and often ends in heart failure. Lack of regeneration in an adult heart is associated with the complexity and inability of cardiomyocytes to divide, along with the absence of adequate muscle-producing cardiac stem cells in the heart.

Cardiomyocytes proliferate extensively during embryonic development but slow dramatically around birth. The growth of heart continues after birth through the increase in cardiomyocyte size, known as hypertropy. This allows DNA synthesis and nuclear division and results in binucleated cardiomyocytes.

Increasing evidence strongly suggests that the human heart shows a degree of cardiomyocyte repopulation (introduction of new cardiomyoctes). It is always challenging to study human heart cellular homeostasis, as it is limited in the availability of human samples and the means to work on it. Who knew nuclear testing during the Cold War would help to uncover dynamics of human cardiomyocyte turnover? Using a technique based on radiocarbon dating of DNA with carbon-14, released from nuclear tests, Bergmann and his colleagues from the Karolinska Institute in Sweden showed that the cardiomyocyte turnover rate is about 1 percent per year at age 20, with a decline to 0.4 percent per year at age 75. This is based on the idea that people born during nuclear tests following World War II until the Limited Nuclear Test Ban Treaty (1963), any cardiomyocyte repopulation should result in lower carbon-14 concentrations. These findings imply that around age 50, about half of the cardiomyocytes in the human heart are generated after birth. However, another study puts emphasis on the importance of cell deaths (apoptosis) for heart cell turnover, asserting that these rates could be much higher (7-40 percent per year). Those findings bring new hopes to heart disease. If the repopulation potential of heart could be therapeutically targeted, the rate of turnover could be extended to overcome the inability to recover cardiomyocyte loss and cardiac contractility after heart attacks.

The better regenerative capacity of fish and amphibians, compared to that of mammals, seems to stem from the presence of species-specific differences. It has been suggested that the limited regeneration potential of mammalian hearts following injury increases survival by prioritizing homeostasis and fibrosis (scar formation by excess connective tissue). Bleeding from the heart in a high-pressure circulation probably favors the more rapid fibrous healing, instead of regeneration, whereas small animals have a low-pressure circulatory system and oxygenation isn’t needed all the time. This phenomenon probably applies to the regeneration of the newborn mouse heart, which also made the removal of the apex of the newborn mouse heart possible.

Cardiac stem cells for regeneration

The heart is a mosaic of various cell types including valvular, arterial, smooth muscle, pacemaker, endothelial, autonomic ganglia, fibroblasts and cardiomyocytes. Those cells have essentially the same genetic makeup but they show a great diversity. Could there be a common cardiac stem cell that gives rise to all those cell types in the heart? There are a number of studies suggesting the presence of such stem cells, though why they fail to regenerate the heart following heart attacks remains unknown.

There have been a number of attempts to discover cardiac stem cells. Some stem cells have been studied in animals and even considered as possible therapies in human trials. Sources of those stem cells could be classifies as resident and non-resident (exogenous) cells of heart. Exogenous stem cell types include skeletal myoblasts, hematopoietic stem cells, mesenchymal stem cells from bone marrow and circulating endothelial cells. Many approaches to identify resident cardiac stem cells are based on knowledge from hematopoietic stem cells. Using surface proteins on the cells known to enrich bone marrow stem cells, several types of resident stem cells are shown to exist in the heart. There are limited improvements in cardiac function using those cells, but the benefits of those cells are thought to be through other mechanisms instead of replacement of dead tissue in the damaged heart.

A study demonstrating the renewal of a newborn mice heart does not completely rule out resident cardiac stem cells as a source of new beating heart cells, but points out the likelihood of their originating from cardiomyocytes by dedifferentiation. Along with a number of attempts to treat heart failure by using stem cells, recent findings offer hope that researchers and doctors will one day able to cure heart disease. Knowing that “there is no disease that God has created, except that He also has created its treatment,” our duty is to study hard and to develop new technologies to find the prospective treatments for heart failure to serve humanity.

References

• Porrello et al. 2011. “Transient Regenerative Potential of the Neonatal Mouse Heart.” Science 25 February: 1078–1080.
• Bergmann et al. 2009. “Evidence for Cardiomyocyte Renewal in Humans.” Science, 3 April: 98–102.
• Charles E. Murry and Richard T. Lee. 2009. “Turnover after the fallout.” Science, V324.
• O.Bergmann et al. 2009. Science 324, 98.
• Simonetta Ausoni and Saverio Sartore. 2009. “From fish to amphibians to mammals: in search of novel strategies to optimize cardiac regeneration.” JBC. 184 (3).
• Martin-Puig et al. 2008. “Lives of a hear cell: Tracing the origins of cardiac progenitors.” Cell Stem Cell 2. April.
• Nevada Nuclear Testing Site: http://mason.gmu.edu/~kcherrix/atomichome.html
• Sahih al-Bukhari, Vol. 7, Book 71.