Stem Cell Discovery Could Aid Scientists In Repairing and Making Organs

By using a mouse model, researchers from the Univ. of Copenhagen have developed an alternative route for cells to follow to build organs. They used this information to attain a stem cell that is new and could possibly generate a supply of organs.

Currently, a stem cell is created by either employing molecules found in pluripotent cells or by placing an embryo in a dish. The process involved reprogramming differentiated cells to create induced pluripotent cells. This new research explores other avenues to make this happen.

The prospect to be able to restore organ tissue that has been damaged is exciting. Researchers are now studying how stem cells create cells of organs like the pancreas, liver, and intestine. In the past, they have tried to copy the process where embryonic cells transform into body parts including organs. Although several attempts have been made it has been very difficult to achieve the lab grown cells to correctly mature. But this new research shows there may be an important step they missed and possibly a different kind of stem cell.

Recently, there have been many studies that have tried to form a gut out of stem cells in a dish. They have now found an innovative way to do this by stem cells following a different path from what happens in an embryo. They discovered a new direction an embryo could take to make organs.

This study primarily focuses on pluripotent stem cells and endoderm extra-embryonic stem cells. A few years ago the team identified a new stem cell line called extra-embryonic stem cells. These stem cells act as key support cells in gastrointestinal organs by supplying membranes and their nourishment and other functions.

By using the alternate path the extra-embryonic stem cells can take, they have the ability to make intestinal organs in the embryo. They then took these stem cells and adapted them into structures that were intestinal organ-like in a dish. From this study, they discovered that when these support cells used this new alternate route, they would actually create organoid structures.

There are certain cells that can potentially be candidates to create organs in the digestive tract, like the pancreas, lung, liver, and intestine. The team were able to label them with a genetic marker. To do this to such a large amount of data required original and new approaches in analyzing the information. Therefore, the team collaborated with physical scientists from the Niels Bohr Institute.

They were able to identify the genes used in the cells. To further aid the work, they developed a computational tool that compared cell clusters. This was used in comparing cells in their dataset and also examine others.

To determine if this new alternate route could create organ cell types they used the extra-embryonic stem cells. They originate at a different place in the embryo then pluripotent stem cells and look like the beginning point for the alternate route for formation of an organ. They were used to develop organ-like structures in the intestines in a dish. They found that both of the routes would work. But using the alternate route could help lab-grown cells from cells that are functional and can study and treat disease.

There is still ongoing research to be done in the details of the function and maturing of these cells. Maybe by using both the traditional route and the alternative route some problems can be solved.

To view the original scientific study click below:
Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics

New Technology to Repair Heart Muscle Cells

A team has reported new technology that will not only repair heart muscle cells in mice, but also can regenerate them after a heart attack. The groundbreaking discovery has the possibility to develop into an important clinical strategy to treat humans who have heart disease.

The brand new technology was developed by researchers using the synthetic messenger ribonucleuic Acid (mRNA) to send mutated transcription factors into mouse hearts. These are proteins that execute the conversion of DNA into RNA. This is the first time this has been done to this degree in research and it has the potential to be a treatment for people.

The team used 2 mutated transcription factors – Stemin and YAP5SA. They worked together to boost the reproduction of heart muscle cells that were isolated from the hearts of mice. The experiments were performed in vitro on dishes of tissue culture.

What they were looking to do was dedifferentiate the cadiomyocyte into a stem cell like existence so that they were able to proliferate and regenerate.

Stemin will turn on properties that are stem like from cardiomyocytes. The discovery of Stemin’s most critical role in the experiments by one of the researchers says the transcription factor is a change in the game. YAP5SA works through promoting growth of organs that will cause the myocytes to copy even more.

From a different discovery the researchers determined that Stemin and YAPS5A repair damage to the hearts in the mice in vivo. Myocyte nuclei reproduced, at minimal, 15 fold in the 24 hour period after heart injections delivered the transcription factors.

When they injected the two transcription factors into infarcted adult mice hearts, the outcome was amazing. The lab discovered myocytes multiplied fast within a day’s time, while hearts over the following month were repaired to an almost normal cardiac function of pumping without much scarring.

An additional benefit of utilizing mRNA, is that it will disappear quickly in comparison to viral delivery. When gene therapies are delivered to cells by viral vectors it raises a variety of biosafety concerns due to they cannot be stopped. Delivery by mRNA turns over quickly and then disappears.

The study is huge in heart regeneration because of the smart strategy of using mRNA to deliver Stemin and YAP5SA. The discovery is particularly important due to less than 1% of adult muscle cells are able to regenerate. Almost all people will die with most of the cardiomyocytes from the first month of life. Following a heart attack the muscle cells of the heart die, and the contracting ability of the heart could be lost.

To view the original scientific study click below:
STEMIN and YAP5SA synthetic modified mRNAs regenerate and repair infarcted mouse hearts

Connection Between Eye Health, Diet & Lifespan Uncovered

A team has demonstrated an association between circadian rhythms, health, diet, and lifespan. It was an unexpected discovery that the fly eye actually drives the process of aging.

Earlier studies have shown in people that there is a link between poor health and eye disorders. The study contends that there is more evidence that dysfunction in the eye can prompt problems in a variety of other tissues. They are now demonstrating that not only will fasting enhance eyesight, but also that the eye will actually play a part that can influence lifespan.

This discovery, in the fruit fly, that the eye itself can directly influence lifespan, surprised the team.

They determined the reason for the link is in circadian clocks, the molecular process within each cell of all organisms. This evolution has adapted to stresses such as variations in temperature and light due to the sun’s rising and setting everyday. These oscillations that occur every 24 hours affect complex behaviors of animals such as prey-predator interactions and the wake/sleep cycles. They also fine tune the temporal modulation of molecular processes of protein translation and gene transcription.

The team showed that fruit flies that are on on restrictive diet had notable shifts in their circadian rhythms and also in extending their lifespan.

A fruit flies lifespan is short which makes it a great model that allowed the team to screen for a variety of things at one time. The study started with a broad survey to determine what genes will oscillate in a circadian fashion when the fruit flies on an unrestricted diet were compared to those that were fed just 10% of the protein of the same diet.

They immediately saw many genes that were diet responsive and in addition exhibited vascillations at different points in time or were rhythmic. They also found that the most activated rhythmic genes from the restrictive diet all seemed to be from the eye, primarily from photoreceptors which are the particular neurons in the retina that are light responsive.

A group of experiments were then done. They were designed to determine how function of the eye can affect how a restrictive diet can extend lifespan. One example was an experiment that showed that keeping the fruit flies in continual darkness seemed to extend their lifespan. This seemed strange to the team. They thought that light was essential for circadian rhythm.

They then utilized bioinformatics to ask the question if the genes in the eye, that are also responsive and rhythmic to dietary restriction, can influence lifespan? Their answer was yes!

We think of the eye as essential for vision. It’s not thought of as something that has to protect that whole organism.

Because the eyes are exposed to everything, the immune defenses are crucially active and can lead to inflammation. If this is present for long time periods, it can lead to or worsen many common diseases that can be chronic. Also, light can cause photoreceptor degeneration which can lead to inflammation.

Constantly looking at phone screens and computers and exposure to light pollution into the night are conditions that are very disturbing to circadian clocks. It can mess up eye protection that could lead to consequences besides just vision and can cause damage to the brain and the body.

There is a lot to understand about the eye’s role in the overall lifespan and health of an organism. This includes asking how the eye can influence lifespan and if the identical effect applies to other organisms?

The most important question that has been raised by this study is how it might apply to people and do photoreceptors in mammals influence lifespan? The team believes probably not as much as is does to the fruit fly, observing that most of the energy in a fruit fly is primarily to its eye. However, since photoreceptors are just specialized neurons, the stronger association is how circadian function plays in neurons in general. This is in particular with restrictions in diet, and how those can be accumulated to maintain nueronal function during the aging process.

Once researchers determine how these processes work, they can start to address the molecular clock to delay aging. It may be that people could maintain vision through activating the clocks that are within the eyes possibly through drugs, diet, and lifestyle changes.

To view the original scientific study click below:
Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster

Transform Stem Cells By Turning Off One Gene

New research from the Univ. of Virginia could assist scientists in understanding how specific genes affect the bodies development. It could show how they play in diseases that are developmental and could possibly help develop new therapies.

A team was able to alter a stem cells course which made them change from turning into heart cells into brain cells just by disengaging one gene.

Previously, it has been understood that the path a cell takes upon changing into a nerve cell or a heart cell is quite rigid. But now the study shows that the process is actually quite fluid.

The method used was CRISPR genome editing to disconnect the Brm gene in the stem cells of mice that were in the process of canalization into heart cells. The result was that the cells of the mice were missing a particular protein known as Brahma. This challenged basic ideas in regards to the stem cells progression to body cells that are mature and it noted that stem cells can be looked at as a blank slate. This is the first to analyze the impact Brahma’s has on cardiac differentiation.

The scientist who made the computer model used in the study, noted the approach was unconventional. Through using the computational models, they got a better perceptive of the Brahma mechanism that can encourage changes in the fate of the cell or the process of differentiation.

There is more to be studied including what happens afterwards and what is the means that these cells turn into highly mature contractile cells? The team believes that there is a significant challenge in this field as to which implications are therapeutic. There is the need to have the ability to develop cells that are mature for transplantation into humans or to develop new drugs.

To view the original scientific study click below:
Brahma safeguards canalization of cardiac mesoderm differentiation

Gene Regulation Could be The Secret of a Longer Lifespan

A team has investigated genes that could be linked to lifespan and has found specific characteristics of certain genes. They have discovered that there are 2 regulatory systems that control gene expression. They are the pluripotency and circardian networks and are crucial to longevity. This information has important implications in the understanding of the evolution of longevity and also in offering new objectives to combat diseases that are age related.

Mammals age at significantly different rates naturally. One of these is the naked mole rat. The mole rat can live up to 41 years, which is nearly ten times longer than similar sized rodents, such as a mouse.

So what is the reason for the longer lifespan? The new research has discovered an important piece to the answer – it could be in the mechanisms that control expression of genes.

The team compared the expression of gene combinations of 26 species of mammals with different maximum lifespans. A shrew was 2 years and the naked mole rate at 41 years. They revealed genes, by the thousands, that were involved to a species’s maximum lifespan were either negatively or positively related to longevity.

They discovered that the species that were long lived usually have gene expression that was low in metabolism of energy and inflammation. The high expression of genes contributed to the repair of RNA transport, repair of DNA, and cellular skeleton organization. Earlier research had shown that attributes such as more effective repair of DNA and a less weak inflammatory response are attributes of mammals that have a long lifespan.

The short lived species had the opposite reaction with high gene expression involved in inflammation and energy metabolism and low gene expression involved in RNA transport, repair of DNA, and skeleton organization.

When the team analyzed the systems that control expression of these genes, they discovered two major systems that play a role. The negative life span gene, which are involved in inflammation and energy metabolism, are regulated by circadian networks. Their expression is confined to a specific time of day which could help control the overall gene expression in the species that were long lived. This means, some exercise can be controlled over the negative lifespan genes.

To live a longer life, we need to curb exposure to light in the evening and have healthy sleep habits, therefore inhibiting the expression of lifespan genes that can be negative.

Positive lifespan genes that are involved in RNA transport, repair of DNA and skeleton organization, are controlled by what is known as the pluripotency network. It involves reprogramming somatic cells. These are any cells that do not reproduce into embryonic cells which can more easily regenerate and rejuvenate by repackaging DNA that has become disorganized through the aging process.

They team found that the pluripotency network evolution is activated to attain longer lifespan.

The pluripotency network and its relation to positive lifespan genes is an important discovery to understand the evolution of longevity. It can show the path for new anti-aging interventions that can activate the main positive lifespan genes. The team expects that successful anti-aging interventions could add to the increase of the expression of lifespan genes that are positive and lower the expression of the lifespan genes that are negative.

To view the original scientific study click below:
Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

Prevention of Inflammation With a Diet Rich in Polyphenols

Foods that contain polyphenols can help counter inflammation in the older population by altering the microbiota in the intestines. They also activate the production of IPA (indole 3-propionic acid), which is a metabolite that comes from the decline of tryptophan caused by bacteria in the intestines.

Polyphenols are compounds that are natural, thought to be probiotics, and are mainly found in vegetables and fruits. A variety of polyphenols in the diet are known to have anti-inflammatory and antioxidant properties. In addition they can interact with gut bacteria to produce postbiotics such as IPA which have positive and beneficial effects on health.

The evidence is increasing verifying that a consistent diet of polyphenols can add to healthy aging. This is especially true if they are also combined with a healthy diet, routine physical activity and no alcohol and tobacco.

The study indicates that gut microbiota and polyphenols interaction can activate the growth of bacteria and is able to synthesize useful metabolites like IPA. This postbiotic has antioxidant, neuroprotective properties, and being anti-inflammatory, contributes to improving intestinal wall health. This compound will help in the avoidance of a variety of diseases that are linked with aging.

In consideration of the favorable effects of IPA on the microbiota in the gut and general health, it is vital to find strategies that can be reliable to enhance the creation of this metabolite.

The team executed a varied analysis to watch the IPA levels in the serum without analyzing the gut microbiota composition. They used fecal samples from 51 participants, 65 and older, who followed a polyphenol rich diet such as bitter chocolate, green tea, and fruits such as blueberries, pomegranates and apples.

The study results indicate that a polypheonol rich diet produced a notable increase in the IPA blood levels and a reduction in levels of inflammation and changes in the microbiota bacteria.

Surprisingly, the team did not notice similar effects in the participants who had kidney disease. This can be explained from the changes in the gut microbiota composition. These participants showed decreased amounts of the IPA at the start of the study in comparison to participants with kidneys that functioned normally.

The results may be relevant clinically because the low levels of IPA have been linked with function of the kidneys rapidly declining and chronic kidney disease.

Therefore, a diet rich in polyphenols including macrobiotic foods could increase the supply of IPA from changes in the gut microbiota composition. Increased levels of a postbiotic, such as IPA in the older population, could be helpful in preventing or delaying chronic diseases that decrease quality of life.

To view the original scientific study click below:
A Polyphenol-Rich Diet Increases the Gut Microbiota Metabolite Indole 3-Propionic Acid in Older Adults with Preserved Kidney Function

Lack of Sleep Can Disrupt Activity in Cornea Stem Cells

A new study has indicated that not getting enough sleep can negatively affect corneal stem cells in both the long term and short term potentially leading to the development of eye disease and impairment of vision.

Failing to get enough sleep is a serious health issue. In the shorter term, the condition can lead to itchy, dry eyes and hyperemia of the eye. Longer term, those who suffer from lack of sleep are at a larger risk of developing eye diseases.

A significant part of good health of the eye is having a cornea that is healthy. The transparent layer of tissue which cover the eye is the cornea. It is maintained by stem cells that are constantly replacing dying cells and mending minor eye injuries. If the corneal processes of the stem cells are dysregulated, a person might develop impaired vision or eye disease.

In the study the team looked at how lack of sleep affects stem cells of the cornea. The study conducted on mice, showed that short term lack of sleep increased the multiplication rate of stem cells of the cornea. Also, there were less antioxidants in the tear film’s composition which is protective. This composition directly affects the activity of the stem cells causing the extra cell multiplication. When eye drops, which contained antioxidants were used, activity of the stem cells returned to their normal rate.

The study suggests that lack of sleep negatively affects stem cells of the cornea which might cause vision impairment on a long term basis. Additional studies are need to confirm these processes occur in human stem cells of the cornea. And other studies are needed to test the effectiveness of local antioxidant therapies in treating health issues with the cornea due to lack of sleep.

To view the original scientific study click below:
Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film

Youthful Function of Old Skin Cells Reprogrammed

Researchers have discovered a new approach that will rejuvenate skin cells. The approach has enabled them to reverse the cellular biological clock by about 30 years based on molecular measures. The cells that were somewhat rejuvenated indicated signs of acting more like cells that were younger in experiments that involved imitating a wound to the skin. The study, still in its early stages, might have indications for regenerative medicine, primarily if it is able to replicate in other types of cells.

The study devised a procedure to “time jump” human skin cells 30 years, which turned back the clock of aging for cells that didn’t lose their specialized function. The work has had the ability to partially restore the behavior of older cells in addition to rejuvenating the molecular measures of biological age. The study while early in exploration, could revolutionize the field of regenerative medicine.

As people age, the function of the cells in our body begin to decline and genome gather aging marks. The goal of regenerative medicine is to replace or repair cells including old ones. An important tool in regenerative biology is the body’s capability to create “induced” stem cells. This process is due to several steps with each deleting a variety of markers that make cells specialized. These cells can possibly turn into any type of cell, but researchers are not able yet to dependently recreate the circumstances that re-differentiate stem cells into all types of cells.

The newest method overcomes the issue of completely deleting the identity of cells by stopping reprogramming part way throughout the process. The team was able to find the perfect balance amid reprogramming cells, thus making them younger biologically yet still able to recapture their specialized objective.

In 2007, the first team turned normal cells which had specific functions into stem cells with specialized capability to develop into any type of cell. The whole process of reprogramming stem cells takes about 50 days utilizing 4 key molecules known as Yamanaka factors. This new method is called “maturation phase transient reprogramming” and exposes cells to the Yamanaka factors for 13 days. Afterwards, changes that are related to aging are eliminated and the cells identity is temporarily lost. The cells that have been partly reprogrammed were allowed time to grow under conditions that were normal to see if their specific function of skin cells (fibroblasts) returned. The results from the genome analysis indicated that cells had retrieved certain markers that were distinctive of skin cells. This was confirmed by observing the production of collagen in the cells that were reprogrammed.

To show the rejuvenation of the cells, the team noticed any changes in aging hallmarks. Their understanding of aging on a molelcular level has advanced over the last few years allowing techniques that scientists can measure age related biological changes in human cells. They had the ability to apply this to their experiment to see if the extent of reprogramming in their new method was achieved.

The team looked at a variety of measures of a cells age. One is the epigenetic clock which is where chemical tags will present throughout the geonome show age. Another is the transcriptome, which is all the gene characteristics which are produced by the cell. Through these measures, the cells that were reprogrammed matched the cell profiles that were 30 years younger when compared to reference data sets.

The possible applications of the method are dependent on the cells not just appearing more youthful, but also functioning like younger cells. Fibroblasts will produce collagen which is a molecule found in skin tendons, bones and ligaments and helps to provide structure for wounds and tissues that are healing. The fibroblasts that were rejuvenated were able to produce extra collagen proteins when compared to controlled cells that didn’t undergo the process of reprogramming.

Fibroblasts will also go into areas that are needing repair. Testing was done on the partially rejuvenated cells through making an artificial cut in cell layers in a dish. They discovered that the treated fibroblasts were able to move into the opening much faster than the old cells. This is an encouraging sign that some day research could create cells that are much better at wound healing.

For the future, the team may find other therapeutic possibilities. They noted that the method can also have an effect on other genes which are related to symptoms and diseases that are age related. The MAF gene plays a role in cataract developmentment, and the APBA2 gene is linked with Alzheimer’s Disease – both indicated changes towards transcription youthful levels.

The mechanism that shows the successful transient reprogramming is not fully understood at this time, and is the next puzzle piece to explore. The team speculates that main areas of the genome which was involved in shaping the identify of the cells might escape the process of reprogramming.

The results show a large step forward to their understanding of reprogramming of cells. They have shown that cells can be rejuvenated and not lose their function and that rejuvenation appears to restore some function to older cells. Observing a reverse in aging indicators in genes linked with diseases is very encouraging for the work’s future.

To view the original scientific study click below:
Multi-omic rejuvenation of human cells by maturation phase transient reprogramming

Exercise That Is Intense May Reduce Fatty Food Cravings

Recent research has offered hope for human dieters. In the study, rats were put on a diet for 30 days and were intensely exercised. The results showed that they resisted cues for normally favored pellets that were high fat. The procedure tested the level of resistance known as “incubation of craving”, which states that the longer a desired item is denied, the more difficult it can be to ignore signals for it.

While more study is necessary, the research does imply that exercise can bolster restraint when it comes to certain food types.

A very integral part of staying on a diet is brain power – being able to say “no” to something a person might be craving but wants to abstain from. Exercise may not only be physically beneficial for loss of weight, it also can mentally help to get control over cravings for foods that are not healthy.

The study included 28 rats that were put through a training. There was a lever that could be pressed to turn on a light and then made a sound before it dispensed a pellet that was high fat. Following the period of training, testing was done to observe how many times the rats would actually press the lever just to get the light and the tone cue.

The team then split the rats into 2 groups – one group was put on a regiment of high intensity running on a treadmill, the other group had no additional exercise besides their current activity. For a period of 30 days both groups were denied access to the pellets that were high fat.

After the 30 day period, the team gave the rats back access to the levers that earlier dispensed the pellets. However, this time when the rats pressed the lever, they only got the light and sound. The rats that were denied any extra exercise now pressed the levers much more than the rats that had been put through intense exercise. This shows that exercise had reduced the desire for the high fat pellets.

In studies in the future the team plans to see the effect of different levels of exercise for this type of craving. In addition, they want to see exactly what happens in the brain with exercise to curb the craving for foods that are unhealthy.

The study is novel, however it does build on work the team did that initially defined “incubation of craving”and has studied other ways to destabilize it. The team leader also credits research that shows exercise can also curb cravings for cocaine.

It is an unsettled study question as to if food can be as addictive as drugs. Not all foods see to have have an effect that is addictive. No one really binges on broccoli for example. But, people do appear to respond to cues such as fast food ads which encourage consuming foods that are high in sugar or fat. These cues might be harder to abstain from the longer they are dieting. Being able to disregard these signals may be another way exercise will improve health.

Exercise is, of course, beneficial in a number of ways. It helps with obesity, cardiac disease and diabetes. It may also help with avoidance of some of the maladaptive foods. People are always looking for a magic pill, and exercise, which is right in front of us, has all these benefits.

To view the original scientific study click below:
Acute high-intensity interval exercise attenuates incubation of craving for foods high in fat

Breathing is the Master Clock of the Sleeping Brain

Neuroscientists have discovered that breathing will coordinate neuronal activity in the brain while it is at rest or sleep.

The brain does not switch off when we are at sleep. Instead, it is saving important memories that happened during the day. For this to occur the regions of the brain syhchronize to coordinate transmission of data between them. But it is still not understood how these mechanisms work. The thought has been that the brain has correlated activity patterns in it. However, the team has shown that breathing will act as a pacemaker that enables these brain regions to synchronize between them.

The most essential and persistent body rhythm is breathing. It exerts a powerful physiological effect on the autonomous nervous system. It also modulates a broad area of cognitive functions which include attention, perception, and thought formation. But the components of its impact on the brain and these functions are mostly unknown.

The team performed in vivo electrophysiological recordings on a large scale in mice including thousands of neuron activity across the limbic system. The results were that respiration coordinates and entrains neuronal activity in all the brain regions investigated. These included the hippocampus, visual cortex, medial prefrontal, thalamus, nucleus accumbens and the amygdala. It did this by regulating the excitability of circuits in an olfaction independent way. They were able to prove the existence of a novel non-olfactory, intracerebral mechanism that accounted for the entrainment of distributed circuits by breathing. They deemed this as “respiratory corollary discharge”.

The findings identify the existence of a link between limbic and respiratory circuits that was currently unknown. This is a deviation from the traditional idea that breathing is modulated by brain activity through the nose-olfactory route.

Coordination of sleep related activity is mediated by this mechanism in brain regions which are important for memory consolidation. It also provides the means for the co-modulation of the cortico-hippocampul circuits synchronous dynamics. These results show a significant step forward to providing the foundation for new theories that will incorporate respiratory rhythm as a fundamental mechanism underlying the communication of distributed systems during consolidation of memory.

To view the original scientific study click below:
Breathing coordinates cortico-hippocampal dynamics in mice during offline states

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