Honeybees may hold the secret to stem cell youth

Royal jelly is a gelatinous substance that honeybees produce to feed their young. This intriguing food also holds the mysterious power of helping some honeybee larvae grow into new queen bees. Some people believe that royal jelly can unlock the fountain of youth. Is there any truth in that?


bee on a flower

New research uncovers some of the 'magical' properties of royal jelly.

In the complex hierarchy of the beehive, the queen bee is the sacred matriarch who keeps the colony alive and organized.

The queen bee lays the eggs from which the larvae will hatch. These larvae later become either the new workers, which are the female bees who do all the work around the hive, or the drones, the male bees whose job it is to mate with the queen.

When a queen bee dies, the colony has to ensure that a new one takes her place.

To produce a new queen bee, worker bees select the most suitable larvae and feed them royal jelly. This will allow one of them to develop into the healthy, strong, and extremely fertile adult female who then becomes the new queen bee.

Royal jelly comprises water, proteins, and sugars, but how exactly it stimulates some larvae to grow into queens rather than worker bees has remained unclear.


Still, due to its seemingly "magical" properties, many people hail this substance as a miraculous ingredient that can boost health and help maintain youth.

In a new study from the Stanford University School of Medicine in California, a team of researchers has decided to investigate how and why royal jelly might be beneficial. They have looked at its effect on one of the most promising targets of clinical research, namely mammalian stem cells. These undifferentiated cells are capable of turning into any specialized cells, serving any function.

"In folklore, royal jelly is kind of like a super-medicine, particularly in Asia and Europe, but the DNA sequence of royalactin, the active component in the jelly, is unique to honeybees. Now, we've identified a structurally similar mammalian protein that can maintain stem cell pluripotency," explains senior author Dr. Kevin Wang.

The researchers tell the story of their current findings in the journal Nature Communications.


The 'magic' ingredient of royal jelly

"I've always been interested in the control of cell size, and the honeybee is a fantastic model to study this," says Dr. Wang. "These larvae all start out the same on day zero, but end up with dramatic and lasting differences in size. How does this happen?"

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In this study, Dr. Wang and his team honed in on a protein called royalactin that is present in royal jelly. They believed that this protein may be, in great measure, responsible for stimulating the impressive cell growth in the larvae that the worker bees select to become queen bees.


In order to study its effects, the researchers decided to apply royalactin to embryonic stem cells, or undifferentiated cells, that they had collected from mice.

"For royal jelly to have an effect on queen development, it has to work on early progenitor cells in the bee larvae," Dr. Wang notes. "So we decided to see what effect it had, if any, on embryonic stem cells," he adds.

Embryonic stem cells are the perfect candidate in clinical research as they have the potential to turn into any specialized cell, playing any role. This potential is called "pluripotency."

Replacing aging, damaged specialized cells with fresh ones that have grown from stem cells has, in theory, the potential to help address any number of diseases. As a result, it is important for researchers to have access to healthy, "youthful" stem cells that they can keep in the labs in their undifferentiated forms until they need to use them.

A protein named 'Regina'

However, Dr. Wang explains, stem cells soon differentiate under lab conditions and become unusable. To keep their pluripotency intact, researchers have had to devise complex inhibitors.

When they added royalactin to embryonic stem cells, the investigators found that it maintained their pluripotency for longer — specifically, for 20 generations — without the need to administer the usual inhibitors.

"This was unexpected. Normally, these embryonic stem cells are grown in the presence of an inhibitor called leukemia inhibitor factor that stops them from differentiating inappropriately in culture, but we found that royalactin blocked differentiation even in the absence of [leukemia inhibitor factor]," Dr. Wang notes.

Still, the researchers did not understand this response. They felt that the mammalian stem cells should not have responded so well to royalactin since mammals do not produce that protein.

They then wondered if they could find a mammalian-produced protein that might match the shape of royalactin rather than its sequence and that may also serve the purpose of sustaining cell "stemness."

Sure enough, they identified a mammalian protein called NHLRC3, which, they thought, may have a structure close to that of royalactin and might serve a similar purpose. NHLRC3, explains Dr. Wang, occurs in all early animal embryos, including those of humans.

When the researchers applied this protein to mouse embryonic stem cells, they found that, like royalactin, it helped maintain their pluripotency. For this reason, the team decided to rename this protein "Regina," which means "queen" in Latin.

"It's fascinating. Our experiments imply Regina is an important molecule governing pluripotency and the production of progenitor cells that give rise to the tissues of the embryo. We've connected something mythical to something real."

Dr. Kevin Wang

In the future, the researchers plan to find out whether Regina can boost wound healing and cell regeneration. They also want to look into more ways of keeping stem cells "youthful" in the laboratory.


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Scientists create human esophagus in stem cell first

Scientists create human esophagus in stem cell first

For the first time, researchers have managed to create a human esophagus in the laboratory. This may pave the way for new, regenerative treatments.

illustration of esophagusThe esophagus runs from the throat into the stomach.

The esophagus is the muscular tube that moves the food and liquids we ingest from our throats all the way to our stomachs.

This organ is made of different types of tissue, including muscle, connective tissue, and mucous membrane.

Scientists at the Cincinnati Children's Center for Stem Cell and Organoid Medicine (CuSTOM) in Ohio have artificially grown these tissues in the laboratory using pluripotent stem cells, or stem cells that can take any form and create any tissue in the body.

The team — which was led by Jim Wells, Ph.D., the chief scientific officer at CuSTOM — grew fully formed human esophagi in the laboratory and detailed its findings in a paper published in the journal Cell Stem Cell. 

To their knowledge, this is the first time that such a feat has been achieved using only pluripotent stem cells.

Laboratory-grown esophagus organoids might help treat a range of conditions, such as esophageal cancer and gastroesophageal reflux disease (GERD).

They may also help treat more rare congenital diseases, such as esophageal atresia (a condition in which the upper esophagus does not connect with the lower esophagus) and esophageal achalasia (wherein the esophagus does not contract and so cannot pass food).

According to recent estimates, GERD — also known as acid reflux — affects around 20 percent of the United States population. In 2018, over 17,000 people in the U.S. will develop esophageal cancer.

As Wells and team explain in their paper, having a fully functional model of the human esophagus — in the form of a laboratory-grown organoid — contributes to a better understanding of these diseases.

The findings may also lead to better treatments using regenerative medicine.

Key protein helps scientists grow esophagus

As they were trying to form the organoids, Wells and team focused on a protein called Sox2 and the gene that encodes it. Previous research had shown that disruption in this protein leads to a range of esophageal conditions.

The scientists cultured human tissue cells, as well as cells from the tissues of mice and frogs, to examine more closely the role of Sox2 in the embryonic development of the esophagus.

The team revealed that Sox2 drives the formation of esophageal cells by inhibiting another genetic pathway that would "tell" stem cells to form into respiratory cells instead.

They also wanted to study the effects of Sox2 deprivation in these key developmental stages. The experiment revealed that the loss of Sox2 resulted in a form of esophageal atresia in the mice.

Finally, they were able to create esophagus organoids that were 300–800 micrometers long at 2 months. The scientists then tested the composition of the laboratory-grown tissues and compared it with that of human esophageal tissue obtained from biopsies.

Wells and team report that the two types of tissue had a very similar composition. Wells comments on the clinical significance of the organoids, saying:

"In addition to being a new model to study birth defects like esophageal atresia, the organoids can be used to study diseases like eosinophilic esophagitis and Barrett's metaplasia, or to bioengineer genetically matched esophageal tissue for individual patients."

"Disorders of the esophagus and trachea are prevalent enough in people that organoid models of human esophagus could be greatly beneficial."

Jim Wells, Ph.D.


via https://www.medicalnewstoday.com/articles/323118.php

What are Stem Cells anyway?

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Sources of stem cells

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic "reprogramming" techniques.

Adult stem cells

Stem cells

Stem cells can turn into any type of cell before they become differentiated.

A person's body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

  • the brain
  • bone marrow
  • blood and blood vessels
  • skeletal muscles
  • skin
  • the liver

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

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Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

Embryonic stem cells

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 3–5 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 4–5 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150–200 cells is the blastocyst. The blastocyst consists of two parts:


  • an outer cell mass that becomes part of the placenta
  • an inner cell mass that will develop into the human body

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

Mesenchymal stem cells (MSCs)

MSCs come from the connective tissue or stroma that surrounds the body's organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Induced pluripotent stem cells (iPS)

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Types of stem cells

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Uses

Transplant with stem cells

Transplants with stem cells are already helping people with diseases such as lymphoma.


Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skin's surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

Cardiovascular disease treatment

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Editionthat they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Brain disease treatment

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinson's and Alzheimer's.

In Parkinson's, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Cell deficiency therapy

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Blood disease treatments

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

Donating or harvesting stem cells

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.


Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

  • the stem cells are easily accessible
  • less chance of transplanted tissue being rejected if it comes from the recipient's own body


What is cord blood banking?What is cord blood banking?Find out more about cord blood banks and how they work.READ NOW

Research and scientific discovery

Stem cell research

Through stem-cell research, scientists hope to discover cures for diseases that are currently incurable.

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Controversy

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

Use of embryos for stem cells

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Mixing humans and animals

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Stem cell therapy and FDA regulation

Some people are already offering "stem-cells therapies" for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

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From https://www.medicalnewstoday.com/articles/323343.php

There Are 'Superbug' Genes in the Arctic. They Definitely Shouldn't Be There.

A "superbug" gene

that was first detected in India — and allows bacteria to evade "last resort" antibiotics — has now been found thousands of miles away, in a remote region of the Arctic, according to a new study.

The findings underscore just how far and wide antibiotic resistance geneshave spread, now reaching some of the most far-flung areas of the planet.

"Encroachment into areas like the Arctic reinforces how rapid and far-reaching the spread of antibiotic resistance has become," senior study author David Graham, a professor of ecosystems engineering at Newcastle University in the United Kingdom, said in a statement. The findings confirm that solutions to antibiotic resistance "must be viewed in global rather than just local terms." [6 Superbugs to Watch Out For]


Not "local" to the Arctic

Antibiotic resistance has existed for much longer than humans have been around. Indeed, bacteria naturally produce substances to defend themselves against other bacteria or microorganisms. (For example, penicillin comes from a type of mold, or fungus.)

But through overuse of antibiotic drugs, humans have accelerated the rate of bacterial evolution, and in turn, the development of antibiotic resistance in these organisms, leading to "a new world of resistant strains that never existed before," Graham said.

One such strain, carrying a gene called blaNDM-1, was discovered in India in 2008. This gene gave bacteria resistant to a class of antibiotics known as Carbapenems, which doctors generally use as a last resort to treat bacterial infections. Since its discovery, the blaNDM-1 gene has been detected in more than 100 countries.

But the researchers were still surprised when it showed up in the Arctic. "A clinically important [antibiotic resistance gene] originating from South Asia is clearly not 'local' to the Arctic," Graham said.

No longer 'pristine'

By traveling to the Arctic, the researchers were actually hoping to get a picture of the types of antibiotic resistance genes that existed before the era of antibiotics. But they found that a slew of modern antibiotic resistance genes were already there.

In the study, the researchers analyzed DNA extracted from soil cores in Spitsbergen, a Norwegian island in the Arctic Ocean. They found a total of 131 antibiotic resistance genes, many of which did not appear to be of local origin.

These genes likely spread through the fecal matter of birds, other wildlife, and human visitors to the area, the researchers said.

But the researchers were still able to find what they were looking for: isolated polar areas where levels of antibiotic resistance genes were so low "they might provide nature's baseline of antimicrobial resistance," Graham said.

Appropriate use of antibiotics in medicine and agriculture is crucial to reducing antibiotic resistance, Clare McCann, lead author of the paper and a research associate at Newcastle University, said in the statement. But she added that it's also critical to understand exactly how antibiotic resistance spreads around the world, including through routes such as water and soil.

The study was published Jan. 27 in the journal Environment International.

Originally published on Live Science.

E-Cigarettes Linked to Heart Attacks, Strokes

Electronic cigarettes are often thought of as "healthier" than conventional cigarettes, but the jury's still out on their potential health risks. Now, a new study has found a link between e-cigarette use and an increased risk of stroke and heart attacks.

The study analyzed information from about 400,000 Americans who took part in a national health survey in 2016. Of these, about 66,800 reported that they regularly used e-cigarettes.

Compared with non-e-cigarette users, regular users had about a 70 percent higher risk of stroke, a 60 percent higher risk of heart attack or angina (chest pain) and a 40 percent higher risk of coronary heart disease.


About 79 percent of e-cigarette users also reported using conventional cigarettes, compared with just 37 percent of non-e-cigarette users. [4 Myths About E-Cigarettes]

But the findings linking e-cigarettes with an increased risk of stroke, heart attack and coronary heart disease held even after the researchers took into account whether people were also conventional cigarette smokers, said study lead author Dr. Paul Ndunda, an assistant professor at the University of Kansas School of Medicine.

What's more, when the researchers analyzed a subset of participants who reported smoking fewer than 100 conventional cigarettes in their lives (meaning they were not regular users of cigarettes), they found that e-cigarette users were still 29 percent more likely to report having a stroke, 25 percent more likely to report having a heart attack and 18 percent more likely to report having coronary heart disease, Ndunda told Live Science.

The findings will be presented next week at American Stroke Association's International Stroke Conference 2019 in Honolulu, but has not been published in a peer-reviewed journal.

The new finding is "quite concerning," said Dr. Larry Goldstein, co-director of the Kentucky Neuroscience Institute at the University of Kentucky, who was not involved with the study. "This is the first real data that we're seeing associating e-cigarette use with hard cardiovascular events" like heart attacks and strokes, Goldstein said in a video interview with the American Stroke Association, which is a division of the American Heart Association (AHA). However, Goldstein noted that the study had limitations. For example, the researchers weren't able to take into account some factors that are known to increase people's risk of stroke and heart disease, such as high blood pressure, alcohol use and an unhealthy diet.

In addition, because the study only examined people's responses at one point in time, it is not able to tease out cause and effect — that is, it cannot prove that e-cigarette use was the cause of people's cardiovascular problems, or whether people who use e-cigarettes have other characteristics that increased their risk.

Still, Goldstein said that these early findings need to be taken seriously, especially given the relatively large percentage of young people who use e-cigarettes. In 2016, about 11 percent of U.S. high school students reported using e-cigarettes in the last 30 days.

Unlike conventional cigarettes, which heat and burn tobacco, e-cigarettes heat up and vaporize a liquid, which usually contains nicotine and other flavorings.

The AHA cautions against the use of e-cigarettes, saying that they may pose health risks that scientists do not yet fully understand. And since e-cigarettes usually contain nicotine, they may get people addicted to the substance, according to the AHA.

Some previous studies have also suggested that the flavorings in e-cigarettes themselves may be harmful. A study published last year in the journal Arteriosclerosis, Thrombosis and Vascular Biology found that e-cigarette chemical flavorings had harmful effects on blood vessel cells in a lab dish.

Originally published on Live Science.