Tag Archives: stem cells

Insulin injection.

Stem-cell implant prototypes pave the way towards life-long treatment for type 1 diabetes

New research is paving the way towards reliable, long-term treatments for type 1 diabetes. The work focused on developing implants based on stem cells that can deliver insulin directly into the bloodstream of diabetes patients.

Insulin injection.
Image credits Peter Stanic.

While the implants are not yet ready for use in a clinical role, the research does prove the viability of such systems for use in the future. The implants consist of pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) and were tested with 26 patients. After more research and development, once such implants become able to secrete levels of insulin that will have a clinical effect on their recipients, they could become a viable alternative to current insulin-delivery systems and islet replacement therapies (pancreatic transplants).

Promising first steps

“The device is band-aid sized and designed to contain the lab grown islet cells for subcutaneous implant. It allows the cells within to become vascularized to permit delivery of oxygen and nutrients and release of insulin into the bloodstream. It is also readily retrievable”, said Dr. Timothy J. Kieffer of the University of British Columbia, corresponding author of the study, for ZME Science.

The team aims to provide an unlimited supply of insulin-producing cells for patients with type 1 diabetes, to mediate continuous, long-term treatment options while minimizing the invasiveness of the procedure.

Insulin is a hormone that keeps the levels of glucose (sugar) in our blood under control, and is produced by pancreatic β-cells. Type 1 diabetes is characterized by the destruction of these cells and leads to dangerously high levels of glucose building up in patients’ bloodstreams. Current treatments for this condition involve the administration of insulin directly into the bloodstream, either via manual injection or through automated systems that a patient can wear, which deliver the hormone periodically. Another possibility — although seen much more rarely in the grand scheme of things — is to treat the condition through islet transplant from donor organs.

Each of these treatment options comes with its own drawbacks. Direct injections require users to monitor their own state, remember to perform the procedure, and also carry the risk that they administer the shots imperfectly. Automated devices can be very burdensome to wear for long periods of time, are associated with long-term complications, and can malfunction. Transplants are very intrusive procedures and the supply of donor organs is very limited compared to the demand.

As such, an alternative is required, the team argues.

The current study reports on a phase I/II clinical trial involving the use of pancreatic endoderm cells as one such alternative. The team’s devices contain such cells in special capsules that allow for direct vascularization of the cells; these were implanted under the skin of the patients. The procedure did, however, run the risk of the participants’ bodies rejecting the implants, and thus involved an immunosuppressive treatment regimen that is commonly used in donor islet transplantation procedures. Possible side-effects of such treatments is an increased risk of cancer and infections in patients, as a direct consequence of their immune systems being suppressed.

That being said, the authors report that the devices worked as intended, and the cells within them started secreting insulin and delivering it directly into the participants’ bloodstreams in response to the glucose levels in their blood. Insulin expression (secretion) was recorded in 63% of the devices after they were explanted at time periods between 3 and 12 months after implantation. Insulin-secreting cells started accumulating progressively in these devices over a period of between 6 and 9 months after implantation.

Although not yet able to cover their full requirements for insulin, over a one-year study period, they reduced the amount of insulin participants needed to be administered by 20%. They also spent 13% more time in the target blood glucose range compared to pre-study periods.

“We found the implants were able to produce insulin in a meal regulated manner like normal healthy pancreatic islets, albeit at low levels,” Dr. Kieffer adds for ZME Science. “The sponsor company ViaCyte recently reported achieving clinically meaningful levels of insulin when more of these devices were implanted (8) that resulted in a dramatic reduction in the insulin injection requirements accompanied by vastly improved control of blood sugar.”

Overall, these devices were well-tolerated by their bodies and there were no severe adverse effects caused by the grafts. Two participants did experience serious adverse effects related to the immunosuppression treatment. Most of the adverse effects reported by participants, however, were related to the actual implantation/explantation surgeries, or to side-effects of the immunosuppressive treatment. All things considered, the team explains, the risk of local infection posed by the devices was very low, suggesting that the devices themselves are well-tolerated even in participants with a poor immune or healing response.

This does raise questions regarding the use of such devices over a patient’s whole life. An ideal solution to this would be an option to perform stem cell-based islet replacement therapy without the devices themselves, as this would bypass the need for immunosuppressive treatments altogether.

Still work to be done

One of the major limitations of the study was the lack of a control group, so the findings should not be used to draw any conclusion on how effective such devices would be at treating type 1 diabetes. However, the study does show that they are relatively safe to use and validate the working principle behind their design. More research will be needed to determine the quantity of cells such implants should contain in order to produce clinically-relevant benefits for patients.

“It was very exciting to see clear meal regulated insulin production in patients following the implants and also see islet cells in the retrieved devices that looked like normal healthy pancreatic islet cells. We now have clear proof of principle data that this stem cell-based approach can work,” Dr. Kieffer adds for ZME Science.

Currently, the cells survive an average of 59 weeks after implantation. The total percentage of insulin-positive cells they contained at maturation was below the team’s ideal target, however. The researchers are now working on solutions to promote vascularization between the grafts and the patients’ bodies, and on measures to improve the survival of the cells they contain.

“Our ultimate goal is to entirely free patients from the burden of glucose monitoring and insulin injections, and without the use of any immunosuppression,” Dr. Kieffer concluded in his email for ZME Science. “We are thus very excited by the recent ViaCyte / CRISPR Therapeutics announcement that Health Canada has approved clinical testing of genetically modified cells that have been engineered to evade detection by the immune system.”

“With protocol refinements and immune-evasive cells, we hope to reach this goal.

The paper “Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes” has been published in the journal Cell Stem Cell.

STEM cells could lead the way towards an effective cure against HIV/AIDS

Stem cells might finally give us the tools to fight off the human immunodeficiency virus (HIV), the pathogen responsible for AIDS, according to a new paper. Although the findings are still quite early, and based on an animal model, the authors are confident that the findings will translate well to human biology.

Image credits Miguel Á. Padriñán.

Researchers at the University of California Davis report that a specialized type of stem cell — mesenchymal stem cells (MSCs) — can boost the body’s immune response against SIV, the simian immunodeficiency virus, in primates. SIV is the equivalent of HIV but only infects non-human primates.

The discovery, they explain, makes it possible for us to establish a realistic roadmap for a multi-pronged HIV eradication strategy.

STEMing the infection

“Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV,” said Satya Dandekar, senior author of the paper and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis. “Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus”.

“We sought to repair, regenerate, and restore the lymphoid follicles that are damaged by the viral infection.”

Lymphoid tissue in the gut is a key site for HIV replication during the early stages of an infection, the team explains, and later forms viral reservoirs that make removing the pathogen very difficult. Previous research has shown that once it gets a foothold here, HIV causes a severe decrease in immune cells in the gut’s mucosal tissues (its lining) and attacks its epithelial barrier lining, causing a leaky gut.

This lymphoid tissue houses structures known as follicles, whose job is to mount long-term counterattacks against pathogens in our bodies by producing antibodies against them. This, unfortunately, means that an HIV infection impairs the same structures that are meant to defeat it.

Antiretroviral drugs are effective in suppressing HIV’s ability to replicate, but they don’t repair the damage the virus already caused to these follicles. So they can keep the infection suppressed, but on their own, they can’t form an efficient treatment against the disease.

However, the team reports that bone marrow-derived MSCs can. They carried out their experiment using a rhesus macaque model that had impaired immunity and disrupted gut functions due to an SIV infection. These cells were able to modulate, alter, and remodel the damaged mucosal site — in essence, they could repair the virus-caused damage.

“We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS,” Dandekar said.

Following the procedure, the authors saw a rapid rise in antibodies and immune T cell levels, both of which engaged with the infection.

Ideally, such approaches would be used in conjunction with current HIV treatments. They can repair our bodies’ natural defenses, while antiretroviral compounds keep the infection in check. That being said, the MSCs were able to improve the hosts’ response against the infection even by themselves.

The paper “Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection” has been published in the journal JCI Insight.

Newborn in Japan receives first treatment with liver STEM cells

A team of doctors in Japan have successfully transplanted stem liver cells into a newborn baby who required transplant, marking a world first.

Stock image via Pxfuel.

This approach could be used in the future for other infants who require organ transplants but are still too young or frail to bear such an intervention, the team explains. The patient suffered from urea cycle disorder, a condition where the liver is not able to break down ammonia, a toxic compound, in the blood, but was considered too small to survive a surgical intervention.

Infant cells to treat infants

“The success of this trial demonstrates safety in the world’s first clinical trial using human ES (embryonic stem) cells for patients with liver disease,” said a press release of Japan’s National Center for Child Health and Development (NCCHD) following the procedure according to todayonline.

At only six days old, the infant (whose sex has hot been disclosed) was too small to undergo a liver transplant, which is not considered safe for patients under 6 kilograms (13 pounds), according to the NCCHD, which usually means they have to be around three to five months old.

However, the baby’s condition would have been fatal until then, so the doctors had to find an alternative way of treatment.

They settled on a “bridge treatment” meant to manage the condition until the baby was big enough for transplant. This procedure involved injecting 190 million liver cells derived from embryonic stem cells into the blood vessels of the liver. And it worked.

They report that the baby “did not see an increase in blood ammonia concentrations” after the procedure and grew up to “successfully complete the next treatment”, namely a liver transplant from its father. The patient was discharged from the hospital six months after birth.

This course of treatment can be used for infant (and perhaps adult) patients who are also waiting for a transplant in other parts of the world. Doctors at the NCCHD note that Europe and the US have a relatively stable supply of liver cells from brain-dead donors, while Japan only has a limited quantity to work with. So they had to use ES cells, which are harvested from fertilized eggs, which has caused some controversy regarding how ethical their use is.

The NCCHD is one of only two organisations in Japan allowed to work with ES cells to develop new medical treatments. It works with fertilised eggs whose use has been approved by both donors having already completed fertility treatment, according to the institute.

The treatment so far isn’t meant to replace transplants, but that’s definitely an exciting possibility for the future. Transplants save lives, but they rely on donors (whose numbers are limited) and require highly specialized equipment, doctors, and medicine to be successful. We can, however, hope that in the future a simple injection may replace the transplants of today.

Canadian researchers develop hand-held skin printer to treat burn patients

Researchers from the University of Toronto (UoT) Engineering and Sunnybrook Hospital, Canada, have developed a new 3D printer that can create sheets of skin to cover large burns and accelerate the healing process.

A simple schematic detailing the use (a) and general structure of the device (b).
Image credits Richard Y Cheng et al., (2020), Biofab.

Nobody likes to get burned — literally and figuratively. So a team of Canadian researchers has developed a handy new tool to take care of our literal burns. This hand-held 3D printer churns out stripes of biomaterial meant to cover burn wounds, promote healing, and reduce scarring. The bio-ink it uses is based on mesenchymal stromal cells (MSCs), a type of stem cell that differentiates into specialized roles depending on their environment.

Don’t feel the burn

“Previously, we proved that we could deposit cells onto a burn, but there wasn’t any proof that there were any wound-healing benefits — now we’ve demonstrated that,” says Axel Guenther, an Associate Professor of Mechanical Engineering at the UoT and the study’s corresponding author.

The team unveiled their first prototype of the printer in 2018. It was quite the novel gadget at the time, the first of its kind to form tissues on-site, deposit them, and have them set in place in under two minutes.

Since then, the team has redesigned the printer 10 times, in an effort to make it more user-friendly and to tailor it to the requirements of an operating room. The current iteration of the design includes a single-use microfluidic printhead (to ensure the part is always sterile), and a soft wheel that’s used to flatten the material and tailor it to wounds of different shapes and sizes.

The MSCs in the ink are intended to promote regeneration and reduce scarring, the team explains. In broad lines, the authors explain, the method is similar to skin grafting, but it doesn’t require for healthy skin to be transplanted from other areas of the patient’s body — it’s printed on the spot. This is especially useful in the case of large burns, they add.

“With big burns, you don’t have sufficient healthy skin available, which could lead to patient deaths,” says Dr. Marc Jeschke, director of the Ross Tilley Burn Centre and study co-author.

The team tested their printer in collaboration with the Ross Tilley Burn Centre and the Sunnybrook Hospital, successfully using the device to treat full-thickness wounds. Such burn wounds involve the destruction of both layers of the skin and often cover a significant portion of the body. While the results were encouraging, the team wants to further refine their printer and improve its ability to prevent scarring.

“Our main focus moving forward will be on the in-vivo side,” explains study leader Richard Cheng, a teaching assistant at the UoT.

“Once it’s used in an operating room, I think this printer will be a game changer in saving lives. With a device like this, it could change the entirety of how we practice burn and trauma care,” adds Jeschke.

The paper “Handheld instrument for wound-conformal delivery of skin precursor sheets improves healing in full-thickness burns” has been published in the journal Biofabrication.

Artificial embryo without sperm or egg forms live fetus

For the very first time, scientists have made artificial embryos from scratch, without sperm or egg, and implanted them into female mice. The embryos developed into live fetuses, but these exhibited major malformations.

Left: a natural 7-day-and-a-half-old embryo implanted in a female mouse. Right artificial 7-day-and-a-half-old embryo implanted in a female mouse with major malformations.

The team at the University of Texas Southwestern Medical Center used extended pluripotent stem cells, which are cells that have the potential, like an embryo, to develop into any type of tissue in the body. These ‘master cells’ are able to form all three major types of cell groups (ectoderm, endoderm, and mesoderm). Unlike simple pluripotent stem cells, the ‘extended’ variety can develop into tissues that support the embryo, such as the placenta. Without this type of stem cells, embryos cannot develop and grow properly.

The researchers coaxed stem cells to form into all the cells required for the development of an embryo by bathing them into a solution made of nutrients, growth stimulants, and signaling molecules. The cells assembled into embryo-like structures, including placental tissue.

Next, the artificial embryos were implanted into the uteruses of female mice. Only 7% of the implants were successful but those embryos that did work actually started developing early fetal structures. There were major malformations, however, as the tissue structure and organization did not closely resemble that of a normal embryo.

Previously, other research groups had managed to grow artificial embryos but this was the first time that they were successfully implanted and developed placental cells.

In the future, the University of Texas researchers plan on refining their method in order to grow fetuses that are indistinguishable from normal ones. The goal is to replace real embryos and make artificial ones at scale. These embryo models could then be grown in dishes to study early mammalian development and accelerate drug development.

Some of the cells that the researchers used to grow into embryos originally came from the ear of a mouse. Theoretically, the same should be possible for human embryos, but why would we? Besides testing drugs, artificial embryos could be grown from the skin cells of an infertile person. Then, in the lab, these embryos could be studied in order to identify potential genetic defects that might cause infertility.

Even if such stem cell-derived embryos do not completely mimic normal embryo growth, there is still a lot we can learn about mammalian development. But, as is always the case with research that breaks the frontiers of what was once thought possible, our policies haven’t yet kept up with advances. There are serious ethical considerations to possibly making a person from a synthetic embryo. Although such a prospect is still science fiction, rapid developments such as the present study suggest that it is not impossible — and we better prepare.

The findings were reported in the journal Cell.

Why do these lab-grown mini-brains emit brain waves?

In what could be a significant finding to understand the development of the human brain, a group of scientists has created miniature brains from stem cells that developed a functional neural network.

A group of stem cells. Credit: Wikipedia Commons

These lab-grown brains are the first observed to produce brain waves that resemble those of preterm babies, despite being a million times smaller than human brains, according to the study, published in the journal Cell Stem Cell.

“The level of neural activity we are seeing is unprecedented in vitro,” says Alysson Muotri, a biologist at the University of California, San Diego. “We are one step closer to have a model that can actually generate these early stages of a sophisticated neural network.”

The pea-sized brains, called organoids, are derived from human pluripotent stem cells. By putting them in a culture that mimics the environment of brain development, the stem cells differentiate into different types of brain cells and self-organize into a 3D structure resembling the developing human brain.

The researchers successfully grew organoids with cellular structures similar to those of human brains. However, none of the previous models developed human-like functional neural networks. Networks appear when neurons are mature and become interconnected, and they are essential for most brain activities.

“You can use brain organoids for several things, including understanding normal human neurodevelopment, disease modeling, brain evolution, drug screening, and even to inform artificial intelligence,” Muotri said.

The team designed a better procedure to grow stem cells, including optimizing the culture medium formula. These adjustments allowed their organoids to become more mature than previous models. They grew hundreds of organoids for 10 months and used multi-electrode arrays to monitor their neural activities.

In order to compare the brain wave patterns of organoids with those of human brains early in development, the team trained a machine-learning algorithm with brain waves recorded from 39 premature babies between six and nine-and-a-half months old.

The algorithm was able to predict how many weeks the organoids have developed in culture, which suggests these organoids and the human brain share a similar growth trajectory. However, it’s not likely these organoids have mental activities, such as consciousness.

“It might be that in the future, we will get something that is really close to the signals in the human brains that control behaviors, thoughts, or memory,” Muotri said. “But I don’t think we have any evidence right now to say we have any of those.”

The team now aims to further improve the organoids and use them to understand diseases associated with neural network malfunctionings, such as autism, epilepsy, and schizophrenia.

“As a scientist, I want to get closer and closer to the human brain,” Muotri said. “I want to do that because I see the good in it. I can help people with neurological conditions by giving them better treatments and better quality of life. But it’s up to us to decide where the limit is.”

Heart balloon.

Heart-repairing patches poised for human trials, researchers report

Heart ‘patches’ developed by the British Heart Foundation (BHF) have proven themselves safe in animal lab trials — and will be moving on human trials.

Heart balloon.

Image credits Peggy Lachmann-Anke , Marco Lachmann-Anke.

The patches could one day help people manage and recover from debilitating heart failure, a condition which affects an estimated 920,000 people in the UK alone, and is on the rise worldwide, say researchers from the BHF. The patches are thumb-sized bits of heart tissue measuring 3cm by 2cm and containing up to 50 million human stem cells. These cells have the ability to turn into fully-functional heart tissue, and are meant to be applied to the heart of someone after they’ve had a heart attack. Used in this fashion, they can limit, and even reverse, the loss of the heart’s pumping ability.

Heart attack, heart defense

“One day, we hope to add heart patches to the treatments that doctors can routinely offer people after a heart attack,” says Dr Richard Jabbour who carried out the research at the London BHF Centre of Regenerative Medicine.

“We could prescribe one of these patches alongside medicines for someone with heart failure, which you could take from a shelf and implant straight in to a person.”

During a heart attack, our hearts’ supply of nutrients and oxygen can become compromised, killing off parts of the heart muscle. This leaves the organ weakened and could even lead to heart failure later on. This condition involves the heart not being able to pump sufficient blood to the rest of the body, making even mundane tasks such as climbing stairs or getting dressed extremely tiring.

The patches are meant to be sewn into place on the damaged heart, where they will offer physical support to the damaged muscle and help it pump more efficiently. At the same time, the patch delivers compounds that stimulate its healing and regeneration. Eventually, the team hopes, these patches will be incorporated into the heart muscle.

The patches start to beat spontaneously after three days, and start to mimic the structure of mature heart tissue within one month, the team explains. After this, they can be grafted into the damaged heart to help it repair and recover normal functionality.

Rabbit trials showed these patches to be safe and that they lead to an improvement in the functioning of the heart after a heart attack. Four weeks after the patches were applied, heart scans showed that the heart’s left ventricle (the one which pumps blood out to the body) was recovering nicely, without any abnormal heart rhythms. Other stem cell delivery methods run the risk of such abnormal rhythms developing, the team explains.

So far, the patches have proven their efficacy. The next steps include a clinical trial with human subjects, first to test how safe they are, then to see if they can achieve the same levels of healing in humans. They were developed as an alternative to the more traditional approach of injecting stem cells directly into damaged hearts, which has had mixed results. In the absence of a patch, the stem cells are quickly cleared from the heart before they can produce any significant repairs.

“One day, we hope to add heart patches to the treatments that doctors can routinely offer people after a heart attack,” says Dr Richard Jabbour, who carried out the research at the London BHF Centre of Regenerative Medicine said.

“We could prescribe one of these patches alongside medicines for someone with heart failure, which you could take from a shelf and implant straight in to a person.”

The findings were presented at the British Cardiovascular Society (BCS) Conference in Manchester on Monday, June 3rd.

Human brain.

Research identifies a gene that makes our brains (and those of primates) unique

Research has identified one gene that makes primate brains unique — including our own.

Human brain.

Image credits John Beal / Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport.

Great apes and humankind owe their high-achieving brains to a single gene. Called PLEKHG6, this gene drives certain aspects of brain development in a different direction in primates as compared to other mammals, the team reports.

Bigger, better, faster brains

“Broadly speaking, this gene can be thought of as one of the genetic factors that make us human in a neurological sense,” says Dr. Adam O’Neill, lead researcher on the study.

The study aimed to determine if primate brains develop differently from those of other animals. The hypothesis was that this leads to higher cognitive power and increased size, but also potential issues tied to the organ’s increased complexity. More to the point, these genetic differences would predispose humans and primates to neurological or psychiatric conditions that other animals are just too simple to develop.

“Such genes have been hard to find,” O’Neill explains, which is why they decided to study sick, rather than healthy, brains. They looked at the genomes of children with a certain brain malformation called periventricular nodular heterotopia. This condition sees a subset of neurons fail to move to their correct spot in the brain as the organ develops, resulting in a range of symptoms such as epilepsy or delayed development.

“We found a ‘damaged’ genomic element in a child that had the attributes of such a primate specific genetic factor,” he explains.

The team used cultured “mini-brains” to study the condition. This technique involved coaxing harvested skin cells to transform into tiny brain-like structures in the lab. All in all, the team found that a particular genetic change in PLEKHG6 which disables one of its components altered the gene’s ability to support the growth and development of stem cells in the brain.

It was previously known that these cells behave differently in primates than other animals, but not which gene regulated their activity, says professor Stephen Robertson, who supervised the research — O’Neill carried it out as part of his Ph.D. at the University of Otago. The present study shows that a particular component of the PLEKHG6 is the regulator and that it was acquired relatively recently in our evolutionary history.

Dr O’Neill says there are very few primate-specific elements in our genome. This discovery adds to a very short list of genetic factors that, at least in one sense, make us human. The work also helps provide more information about the list of genes that are altered to cause this particular type of brain malformation.

“Such an understanding positions us to better understand how a brain builds itself- knowledge that will add to our ability to design strategies to repair the damaged brain, especially early in infancy where there are still lots of stem cells around,” he says.

“Personally, I also think it does underscore how it is very subtle nuanced differences that separate us from other animals. Our anthropocentrism could be a whole lot more humble.”

The paper “A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration” has been published (PDF link) in the journal Cell Reports.

Cells

5 Technologies Scientists Are Currently Pursuing to Improve Healthspan

Cells

Credit: Pixabay.

During the 20th-century, lifespan in the United States increased by more than 30 years, of which 25 years can be attributed to advances in public health. But while people nowadays are living longer than they ever have in the history of modern civilization, that doesn’t mean that these extra decades are spent in good health.

People have always been looking for a fabled “Fountain of Youth” in some form or the other. No one likes the idea of growing old, which is why It’s no wonder that the global anti-aging market was worth $250 billion in 2016 and is estimated to reach $331.41 billion by 2021. Products in this niche include cosmetic treatments, hormone replacement therapies, implants, prosthetic devices and stem cell treatments. However, the anti-aging industry is rife with advertisements of questionable claims. Many of these treatments are unregulated, clinically unproven, and even potentially harmful, which is ironic seeing how something which was supposed to slow aging may actually accelerate it by making people ill. To date, there is no medicine proven by a clinical trial that can slow down biological aging — but there are some signs that it may be possible.

Recent developments in genetic and cellular research suggest that we may want to focus on how well we live as opposed to how long we live. It’s all about healthspan, not lifespan. Here are some of the most interesting research that scientists are currently pursuing.

Transfusion of young blood

It sounds like the plot of a bad vampire movie but some scientists are truly exploring the rejuvenating effects of transfusing blood from younger individuals. The idea of refreshing old blood with new blood was pioneered by Clive McCay of Cornell University and dates back to the 1950s, when the researcher stitched together the circulatory systems of an old and young mouse. The technique, which is called parabiosis, caused the cartilage of the old mouse to appear much younger than expected.

It wasn’t until much later that researchers were able to find some of the mechanisms responsible for this rejuvenating action. Since McCay’s original research, studies have shown that parabiosis rejuvenates the liver, skeletal stem cells, improves cognition, and reverses heart decline in older mice. A protein called GDF11 found in blood plasma seems to be responsible for some of the rejuvenating effects, as identified by Harvard researchers in 2012. In both mice and humans, GDF11 levels fall with age. We don’t know why this happens yet but there are hints that the decline occurs due to growth control mechanisms.

These fascinating results suggest that a similar rejuvenating effect might be possible in humans, as well. In October 2014, researchers at Stanford transfused young blood to older patients with mild/moderate Alzheimer, but the results have not been published yet, as patients need to be monitored for a long period of time. Meanwhile, a startup called Ambrosia is already offering plasma infusions at $8000 for two liters, to anyone aged over 35. However, be warned that such procedures have not yet been verified by science. Actually, there are even quite a few ‘snake oil’ ploys centered around young-blood transfusion, as reported by Scientific American.

Senolytics that kill old cells

Scientists have been testing the effectiveness of a class of small molecules called senolytics, which kill senescent cells — those that have stopped dividing due to DNA mutations and other damage.

Senescent cells secrete large amounts of some proteins that are harmful to their neighbors, stimulating excessive growth and degrading normal tissue architecture. These cells have also been associated with cancer and release chemicals that cause inflammation.

Senescent cells are still alive, it’s just that they stop functioning properly.

In a study published this year, researchers at the Mayo Clinic in Rochester used a combination of dasatinib and quercetin (D+Q), which killed senescent cells and slowed the deterioration in walking speed, endurance, and grip strength in mice. Previously, when the researchers injected young (four-month-old) mice with senescent cells, the mice began to show impaired physical function, such as maximum walking speed, muscle strength, physical endurance, daily activity, food intake, and body weight.

“This is exciting research,” said Felipe Sierra, Ph.D., director of the National Institute of Aging’s Division of Aging Biology. “This study clearly demonstrates that senolytics can relieve physical dysfunction in mice. Additional research will be necessary to determine if compounds, like the one used in this study, are safe and effective in clinical trials with people.”

NAD+ boosting supplements

Scientists have become increasingly interested in the coenzyme nicotinamide adenine dinucleotide, or NAD+, which plays a very important role in the biological functions that make life possible. NAD+ is crucial to turning nutrients into energy in metabolism, as well as other processes like maintaining healthy DNA and regulating circadian rhythms. A number of studies have demonstrated that increasing NAD+ levels in mice can, for example, restore muscle function and enhance regeneration in the brain. Now scientists are looking to translate this research to humans.

A clinical trial, which involved 60- to 80-year-olds over an eight-week period, found NAD+ levels could be increased by an average of 40 percent at a standard dose of 50 mg of pterostilbene (an antioxidant found in blueberries) and 250 mg of NR, a day. This was the first trial to show it was possible to elevate NAD+ levels sustainably over a period of time.

Although you can already order an NAD+ supplement, more studies will have to be undertaken before any conclusive claims about NAD+ and its rejuvenating properties can be made.

Stem cell therapy

The number of stem cells in our body tends to decrease with age. Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types — they’re sort of like the body’s raw materials.

Stem cells are important because they provide new cells for the body as it grows, and replace specialized cells that are damaged or lost. Doctors hope to use stem cells in a guided fashion in order to replace diseased cells and organs.

Mesenchymal stem cells (MSCs) are a particular type of adult stem cell generating a great deal of interest in the world of science. Currently, they’re being used to treat a wide range of diseases from cancer to heart disease, but new research is starting to discover their anti-aging properties as well. A 2017 clinical trial on humans, 15 frail patients with an average age of 76 received a single MSC infusion collected from bone marrow donors aged between 20 and 45 years old. After six months, all patient showed improvements in fitness and an overall improvement in their quality of life.

Researchers at the Albert Einstein College of Medicine in New York found that the hypothalamus — a small portion of the brain that plays a crucial role in many important functions, such as releasing hormones. regulating body temperature —  releases hormones that affect other organs, affecting how mice age. By injecting the hypothalamus with extra stem cells, taken from the brains of newborn mice, the researchers slowed down aging and gave mice an extra two to four months of life — that’s a 20% lifespan increase.

That being said, stem cells therapy for anti-aging or rejuvenating properties is still classed as experimental and people should shy away from “stem-cell-based” topical creams and stem-cell­-injection clinics.

The longevity gene

A study of Amish people found that a subgroup of people with a single mutation in the SERPINE1 gene lived to 85 years, on average — significantly longer than the predicted lifespan of 71 years for the general Amish population. The mutation significantly lowers the production of a protein called PAI-1, and this may explain the tendency to be in better health with advancing age.

A lower PAI-1 protein count in their body seems to make individuals more resilient in the face of disease. According to the researchers, Amish people with the SERPINE1 mutation had no signs of diabetes as opposed to 7 percent of the Amish individuals with the normal SERPINE1 gene. What’s more, those with the mutation also exhibited a better metabolism and lower-than-average levels of fasting insulin, according to the findings published in Science Advances.

Previously, Israeli researchers identified another gene mutation that extends lifespan, also by ten years, but only in men.

Since there aren’t any apparent negative effects related to PAI-I deficiency, it’s possible to use drugs to target this protein. Already, Japanese researchers at Tohoku University are conducting an early phase clinical trial with an orally active PAI-1 blocker. A Japanese company called Renascience holds the patent for the drug which is currently being licensed to Eirion Therapeutics in the United States. There, the drug is marketed as a treatment for baldness since one of the mechanisms by which PAI-1 contributes to aging is by limiting cell mobility, which can be important in hair growth.

 

Doctors restore patient’s sight with stem cells, offering new hope for cure to blindness

Scientists have developed a specially engineered retinal patch to treat people with sudden, severe sight loss.

The macula lutea (an oval region at the center of the retina) is responsible for the central, high-resolution color vision that is possible in good light; when this kind of vision is impaired due to damage to the macula, the condition is called age-related macular degeneration (AMD or ARMD). Macula lutea means ‘yellow spot’ in Latin.

Picture of the back of the eye showing intermediate age-related macular degeneration.
Via Wikipedia

Douglas Waters, an 86-year-old from London, had lost his vision in July 2015 due to severe AMD. After a few months, Waters became part of a clinical trial developed by UC Santa Barbara researchers that used stem cell-derived ocular cells. He received his retinal implant at Moorfields Eye Hospital, a National Health Service (NHS) facility in London, England.

Before the surgery, Water’s sight was very poor, and he wasn’t able to see anything with his right eye. After the surgery, his vision improved so much that he could read the newspaper and help his wife in the garden.

The study, published in Nature Biotechnology, shows groundbreaking results. Researchers could safely and effective implant a specially engineered patch of retinal pigment epithelium cells derived from stem cells to treat people with sudden severe sight loss from wet AMD. This is the first time a completely engineered tissue has been successfully transplanted in this manner.

“This study represents real progress in regenerative medicine and opens the door on new treatment options for people with age-related macular degeneration,” said co-author Peter Coffey, a professor at UCSB’s Neuroscience Research Institute and co-director of the campus’s Center for Stem Cell Biology & Engineering.

Douglas Waters was struggling to see up close after developing severe macular degeneration, but 12 months on he is able to read a newspaper again

AMD usually affects people over the age of 50 and accounts for almost 50% of all visual impairment in the developed world. The condition disturbs central vision responsible for reading, leaving the surrounding eyesight normal. Wet AMD is caused by hemorrhage or liquid accumulation into the region of the macula, in the center of the retina. Wet AMD almost always starts as dry AMD. Researchers believe that this new technique will be the future cure for dry AMD.

Scientists wanted to see whether the diseased retinal cells could be replenished using the stem cell patch. They used a specially engineered surgical tool to insert the patch under the affected retina. The operation lasted almost two hours.

Besides Water, another patient, a 60-year-old woman who also suffered from wet AMD, underwent the surgery. The two patients were observed for one year and reported improvements to their vision. The results were incredible — the patients went from being almost blind to reading 60 to 80 words per minute with normal reading glasses.

“We hope this will lead to an affordable ‘off-the-shelf’ therapy that could be made available to NHS patients within the next five years,” said Coffey, who founded the London Project to Cure Blindness more than a decade ago.

 

 

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

Scientists make transparent bones to study diseases like osteoporosis

Every bone in your body no older than ten years despite how old you might actually be. Just like skin, bone sheds old tissue and grows a new one from stem cells sourced from the bone marrow. Some scientists say that observing how these stem cells interact when they transform into bone tissue could lead to new treatment and drugs for diseases such as osteoporosis. Imaging stem cells inside bones, however, has always proven challenging — until now. Remarkably, American researchers recently showed how to grow intact and transparent bones.

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

You don’t feel like your bones are changing because the process involves a delicate interplay of cells that build new bone mass and cells that break down old bone mass. This continual remodeling cycle is controlled by stem cells called osteoprogenitors that develop into osteoblasts or osteocytes. These cells are what regulate and maintain the skeleton. This is why scientists find it crucial to understand how these stem cells behave when new bone mass is created. But this isn’t easy. Bones don’t lie but they sure don’t give up secrets easily. The stem cells are pretty rare and not evenly distributed throughout the bone.

To determine stem cell populations in the bone, researchers usually slice the bone into thin sections then extrapolate the number of stem cells. Not only does this method introduce a lot of uncertainties, the slicing also deteriorates the bone. Being able to peer inside the bone somehow is thus very desirable in the field.

A while ago, Viviana Gradinaru, assistant professor of biology and biological engineering at CalTech, helped develop a technique called CLARITY which can render soft tissue like the brain transparent. It manages this through the removal of lipids from cells which cause tissue to be opaque. Additionally, a clear hydrogel mesh is infused to provide structural support. The approach is so effective that at one point, while working as a post-doc at Stanford University, Gradinaru and colleagues were able to make all of the soft tissue inside a mouse transparent.

Now at CalTech, Gradinaru’s lab expanded the method so it works for hard tissue as well. The team first started with bones from postmortem transgenic mice which were genetically engineered to have red fluorescent stem cells so these could be more easily identified. The types of bones selected for the study were the femur and tibia, as well as some bones of the vertebral column. No bone was longer than a few centimeters, that’s for sure.

After they removed the calcium molecules from the bones which contribute to opacity, the team infused the bones with a hydrogel that locks cellular components in place and preserve the architecture of the sample. The last step involved using a detergent to flush away the lipids, leaving a transparent bone instead, as reported in Science Translational Medicine.

To image the cells inside the bones properly, a custom light-sheet microscope for fast and high-resolution visualization was employed. This instrument does not damage the fluorescent signal.

Already, the Bone CLARITY method is being used in collaboration with a biotech company to test a new drug for osteoporosis. The condition occurs when loss of bone mass leads to a high risk of fractures and affects millions of Americans yearly.

 

“Biologists are beginning to discover that bones are not just structural supports,” says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. “For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs.”

Mouse pups born from eggs released by lab-grown ovaries. Credit: O. Hikabe et. al.

Mouse eggs engineered entirely in the lab for the first time — later lead to healthy adults

Mouse pups born from eggs released by lab-grown ovaries. Credit: O. Hikabe et. al.

Mouse pups born from eggs released by lab-grown ovaries. Credit: O. Hikabe et. al.

A paper that has been met by everyone in the field with cheerful enthusiasm describes how the authors grew mice eggs from the ground up, starting from stem cells. The eggs were then fertilized with sperm and implanted in foster mothers. Though the success rate was less than 1%, some of the embryos grew into healthy pups and later into adults with no sign of dysfunctionality. The implications for fertility, but also the prospect of designer babies, are staggering.

From cell to egg to living mammal

The landmark procedure was performed by Katsuhiko Hayashi and colleagues at Kyoto University in Japan and took a decade to shape. At first, they started by coaxing pluripotent stem cells — cells that resemble stem cells and which theoretically can differentiate into any kind of cell in the body — to turn into egg and sperm cells.

In 2012, the Japanese researchers showed they could make fertile eggs from both mouse embryonic stem (ES) cells and induced pluripotent stem cells (iPS). While these iPSCs are similar to embryonic stem cells, the key difference is that they can be made from any cells from the host, like the skin. Pluripotency implies the capacity for stem cells to become a number of different cell types, but that does not necessarily provide the ability to develop an entire organism.

The discovery of induced pluripotent cells is one of the most important breakthroughs in biology because it means that you can now grow an entire liver or kidney that is biocompatible with the patient. In this case, the donor is the patient himself and millions of lives could be saved in the future once scientists get the knack of growing whole, functioning organs in the dish.

But going back to our mice and eggs, it was only this summer that Hayashi and colleagues fitted one of the last pieces of their jigsaw puzzle when they grew mouse ovaries in the lab, then used them to produce fertile eggs.

In total, around 50 eggs were produced, granted many presented chromosomal abnormalities. Still, 75% of the eggs had the correct number of chromosomes and these were mixed with sperm to produce 300-celled embryos.

The embryos were then implanted into foster mothers, but only 11 or 3% grew into full-term pups compared to 62%, in the case of eggs taken from adult mice and fertilized in vitro. The pups that did survive, though, grew into functioning adults.

“This is truly amazing,” says Jacob Hanna, a stem cell biologist at the Weizmann Institute of Science in Rehovot, Israel.  “To be able to make robust and functional mouse oocytes over and over again entirely in a dish, and see the entire process without the ‘black box’ of having to do any of the steps in host animals, is most exciting.”

“Parts of this work were done before — here they are put together in completeness. It’s impressive that they got pups that way,” says Dieter Egli, a stem cell biologist at the New York Stem Cell Foundation Research Institute.

The low success rate means we won’t be seeing human babies born this way anytime soon, but the paper demonstrated a way for infertile women to have their own babies. Another more ethically challenged pathway is that we could one day use this method to make designer babies starting from nothing but a few skin cells, with specific genetic alterations using a tool such as CRISPR-CAS9.

Both scenarios are very far away from becoming reality. The possibilities they entertain can only boggle the mind, though.

Scientists use embryonic stem cells to create bone, heart muscle in just 5 days

Researchers from Stanford University have quickly and efficiently created pure populations of 12 different cell types – including bone, heart muscle and cartilage – from ancestral embryonic stem cells.

Image credit Pixabay

Image credit Pixabay

Stem cells of these cell types have been created in the past, but the current study marks the first time that pure populations have been created in a matter of days as opposed to weeks or months. In addition, previous techniques typically led to impure mixtures that contained multiple cell types, limiting their practical use.

“Regenerative medicine relies on the ability to turn pluripotent human stem cells into specialized tissue stem cells that can engraft and function in patients,” said Irving Weissman, the director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “It took us years to be able to isolate blood-forming and brain-forming stem cells.”

“Here we used our knowledge of the developmental biology of many other animal models to provide the positive and negative signaling factors to guide the developmental choices of these tissue and organ stem cells,” he added. “Within five to nine days we can generate virtually all the pure cell populations that we need.”

Embryonic stem cells are pluripotent, meaning they have the ability to form into any cell type in the body. This process is guided by various time- and location-specific cues that occur within the embryo, ultimately pushing their development in the direction of a specific cell type. Scientists understand a lot about how this process is guided in animals such as fish, mice, and frogs, but due to the restrictions on human embryo cultivation, they know little about human embryonic development.

In the new study, the team learned that human stem cells move down a developmental path that is composed of a series of choices that present just two possible options. They found that the best way to guide these cells towards a particular fate was to encourage the differentiation into one lineage and at the same time block the other pathway. In other words, saying “yes” to one choice while simultaneously saying “no” to the other.

“We learned during this process that it is equally important to understand how unwanted cell types develop and find a way to block that process while encouraging the developmental path we do want,” said Kyle Loh, co-lead author of the study, which was published July 14 in the journal Cell.

Through careful guidance of the developmental pathway, Loh and the team were able to push stem cell differentiation in the direction that they wanted, leading to the creation of 12 different cell lineages in a quick and effective manner.

“Next, we’d like to show that these different human progenitor cells can regenerate their respective tissues and perhaps even ameliorate disease in animal models,” he said.

rabbit eye

Eye tissue grown from scratch in the lab used to restore sight to blind rabbits

Coxing cells to multiply and grow into any type of tissue is one of the most mind boggling, yet challenging science. It’s well worth it once you’ve got everything pinned down. Just remember complex organisms like us humans started with with one single cell, and unlocking this potential bred and nurtured by millions of years of evolution might be limitless. One prime example of what you can do with stem cells comes from Japan where researchers made all the important distinct tissues that makeup the eye. Corneas made by them were transplanted to blind rabbits. The animals could see afterwards.

rabbit eye

Image: Pixabay

“We are now in the position to initiate first in-human clinical trials of anterior eye transplantation to restore visual function,” Kohji Nishida, a biologist at Osaka University in Japan, wrote in the paper he co-authored in Nature.

In 2006, Shinya Yamanaka made a groundbreaking discovery that would win him the Nobel Prize in Physiology or Medicine just six years later: he found a new way to ‘reprogramme’ adult, specialized cells to turn them into stem cells. These laboratory-grown stem cells are pluripotent – they can make any type of cell in the body – and are called induced pluripotent stem cells, or iPS cells.  Before this remarkable discovery, embryonic stem cells were the only pluripotent cells available.

Both iPS and embryonic stem cells  are self-renewing, meaning they can divide and produce copies of themselves indefinitely. Now, using a couple of skin samples researchers can re-program them into iPS, which in turn can be induced to grow into a liver or neurons for instnace. It’s that versatile.

To study diseases, iPS disease are proving to be more and more valuable. Instead of using animal models, like the lab mouse, researchers can now, say, grow  genuine brain cells from patients with Parkinson’s disease, especially in the early stages of the disease before the patient is aware of any symptoms. The neurons have the same genetic background (the same basic genetic make-up) as the patients’ own cells. Thus scientist can directly work with neurons affected by Parkinson’s disease in a dish.

Reprogramming holds great potential for new medical applications, such as cell replacement therapies. Since iPS cells can be made from a patient’s own skin, they could be used to grow specialized cells that exactly match the patient and would not be rejected by the immune system. Whole specialized tissue or organs can be also be made.

Nishida and colleagues, for instance, coerced iPS cells to form a simple proto-eye, complete with all important tissues. This includes the retina —  the light-sensitive layer of tissue at the back of the eyeball. The iPS cells were made from rabbit skin cells.

Clear sheets of corneal material were grafted from the eye grown in a dish and implanted into the eyes of rabbits with defect corneas from birth. The animals could see following the operation.

The major breakthrough lied in the fact that these tissues could be controlled and grown separately.

“Our work not only holds potential for developing cells for treatment of other areas of the eye, but could set the stage for future human clinical trials of anterior eye transplantation to restore visual function,” the researchers wrote.

Clinical trials will start soon and hopefully the same technique might be used soon to restore vision to humans with damaged corneas. So far, it all looks very promising and there’s no technical reason why this shouldn’t work. Recently, scientists in China repaired the eyes of 12 children under two years old with cataract by using stem cell therapy.

 

 

 

restored_cornea

Better, simple way to regrow damaged corneas shines hope for blind patients

restored_cornea

A restored, functioning cornea found in a mouse, that used human harvested limbal stem cells. Image:  Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank

A novel and highly effective technique was found to enhance regrowth of human corneal tissue to restore vision, using a newly identified molecule that acts as a marker for limbal cells – stem cells that are paramount to retinal regeneration. The findings could greatly improve the vision of patients suffering from severe burns, victims of chemical injury, and others with damaging eye diseases.

Eyeing elusive stem cells

A healthy, transparent ocular surface is made up of non-keratinized, stratified squamous epithelium that is highly differentiated. The corneal epithelium is constantly renewed and maintained by the corneal epithelial stem cells, or limbal stem cells (LSCs) that are presumed to reside at the limbus, the junction between the cornea and conjunctiva. Patients who have lost these special stem cells due to disease or injury typically go blind. In fact, there are over 3.2 million people worldwide recognized as bilateral blind from corneal diseases, most of which were struck by limbal stem cell deficiency (LSCD).

Typically, doctors use tissue or cell transplants to help the cornea regenerate, but since they never know whether there are any actual limbal stem cells in the grafts, or how many, the results have always been inconsistent. A new collaborative effort that joins scientists from the Massachusetts Eye and Ear/Schepens Eye Research Institute, Boston Children’s Hospital , Brigham and Women’s Hospital, and the VA Boston Healthcare System may change this.

 In this study, researchers were able to use antibodies detecting the marker molecule to zero in on the stem cells in tissue from deceased human donors and use it to regrow anatomically correct, fully functional human corneas in mice.

In this study, researchers were able to use antibodies detecting the marker molecule to zero in on the stem cells in tissue from deceased human donors and use it to regrow anatomically correct, fully functional human corneas in mice.

The researchers found that an antibody, known as ABCB5, was being produced in tissue precursor cells in human skin and intestine. Tests on a mouse model showed ABCB5 also occurs in limbal stem cells and is required for their maintenance and survival, and for corneal development and repair. Essentially, ABCB5 can be used as an effective marker to zero in on the limbal stem cells. For instance, mice lacking a functional ABCB5 gene lost their limbal stem cells, and their corneas healed poorly after injury.

“Limbal stem cells are very rare, and successful transplants are dependent on these rare cells,” said Bruce Ksander of Mass. Eye and Ear, co-lead author on the study with postdoctoral fellow Paraskevi Kolovou. “This finding will now make it much easier to restore the corneal surface. It’s a very good example of basic research moving quickly to a translational application.”

Using ABCB5 antibodies, the researchers successfully identified the LSCs in tissue from deceased human donors, then used these to regrow anatomically correct, fully functional human corneas in mice.

“ABCB5 allows limbal stem cells to survive, protecting them from apoptosis [programmed cell death],” said Markus Frank. “The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general,” according to Natasha Frank.

Photo: University of Utah Health Sciences

Mice with multiple sclerosis walk and run again after human stem cell treatment

In a feat that surprised even the scientists who made the experiment, mice disabled by a condition similar to multiple sclerosis (MS) began to walk and even run again after human stem cells had been transplanted. The findings could potentially offer new means of treating MS, a terribly disease which plagues some 2.3 million people worldwide.

Photo: University of Utah Health Sciences

Photo: University of Utah Health Sciences

Growing stem cells and new legs

University of Utah researchers first transplanted human stem cells with no particular beneficial expectations. The scientists thought the stem cells would be rejected in the first place, like most foreign cells by the host’s immune system, however something much more than this happened. The plagued mice began to walk again within a short period, 10 to 14 days, following the transplant.

“My postdoctoral fellow Dr. Lu Chen came to me and said, ‘The mice are walking.’ I didn’t believe her,” said co-senior author, Tom Lane, Ph.D., a professor of pathology at the University of Utah, who began the study with co-first author Chen at the University of California, Irvine.

Multiple sclerosis (MS) is a potentially debilitating disease in which your body’s immune system eats away at the protective sheath (myelin) that covers your nerves. Damage to myelin causes interference in the communication between your brain, spinal cord and other areas of your body. This condition may result in deterioration of the nerves themselves, a process that’s not reversible.

Current treatments and drugs only concentrate on halting any of disease’s progress or ameliorating symptoms; once MS is in a later stage, it can not be reversed and there is no cure. Results from the study demonstrate the mice experience at least a partial reversal of symptoms. Immune attacks are blunted, and the damaged myelin is repaired, explaining their dramatic recovery.

“The way we made the neural stem cells turns out to be important,” said Loring, describing the reason behind the novel outcome.

The human neural stem cells send chemical signals that instruct the mouse’s own cells to repair the damage caused by MS. Experiments by Lane’s team suggest that TGF-beta proteins comprise one type of signal, but there are likely others. This realization has important implications for translating the work to clinical trials in the future.

“Rather than having to engraft stem cells into a patient, which can be challenging from a medical standpoint, we might be able to develop a drug that can be used to deliver the therapy much more easily,” said Lane.

Next, the researchers need to assess the long term effects of the human stem cell transplanted mice.

“We want to try to move as quickly and carefully as possible,” Lane continued. “I would love to see something that could promote repair and ease the burden that patients with MS have.”

Findings appeared in the journal Stem Cell Reports.

oldest woman in the world

Blood from world’s oldest woman tells us why life reaches its limits

oldest woman in the world

Hendrikje van Andel-Schipper, aged 115. Photo: wikia.com

No matter how much some would like to avoid this prospect, death is inevitable for all living beings (or is it?). Yet, some people at least live longer than others. A great deal of attention has been drawn to longevity for obvious reasons, but any effort to prolong life needs to start with the very root of the problem – death. So, why do people die of old age? What are the underlying processes? Scientists in Netherlands found invaluable clues as to how our bodies steadily succumb to the inevitable, ultimate end after studying blood and tissue collected from who was once the world’s oldest woman.

World’s oldest woman

There aren’t too many people today who can boast they lived in the IXXth century, but  Hendrikje van Andel-Schipper, born in 1890, was one of them. She was the world’s oldest woman, before she unfortunately passed away in 2005, but what’s truly remarkable isn’t the number of days and nights in her life, but how she lived these days – quality vs quantity. Until her very last days, the woman had a crystal clear cognition, according to her doctors and family, and lived a vigorous and independent life. At 115 year, this comes as an astonishing fact.

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Sane as she was at her old age and aware of her privileged status, van Andel-Schipper chose to give her body to science, allowing for any necessary measures to study it that might help scientists understand how she reached her centenarian years. The findings suggest that our lives are limited by  the capacity for stem cells to keep replenishing tissues day in day out. As these stem cell exhaust their ability to replenish cells, we age and eventually die as this replenishing rate reaches its limit.

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For instance, Dutch researchers found after analyzing van Andel-Schipper’s blood that two-thirds of the white blood cells originated from just two stem cells. When a cell replicates, it has a pattern of mutation which also applies to white blood cells. The pattern was so similar in all cells that the researchers could conclude that they all came from one of two closely related “mother” stem cells.

“It’s estimated that we’re born with around 20,000 blood stem cells, and at any one time, around 1000 are simultaneously active to replenish blood,” says Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, who headed the research team.

Considering all these white blood cells came from just two stem cells, it’s safe to assume that most of the stem cells she started out with in life faded away, withered and died. Also, besides stem cell count, telomere length is also of key importance.

Life’s too short

Telomeres have been compared with the plastic tips on shoelaces, because they keep chromosome ends from fraying and sticking to each other, which would destroy or scramble an organism’s genetic information. Yet, each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive or “senescent” or it dies. This shortening process is associated with aging, cancer, and a higher risk of death. So telomeres also have been compared with a bomb fuse.

In Andel-Schipper’s case, her white blood cells had drastically worn out telomeres – 17 times shorter than those on brain cells, which hardly replicate at all throughout.

Other important insights came as researchers studied telomeres and stem cells. Invariably, the researchers had to look at cell mutations and this is the first time something like has been performed on a person this old. One reason she grew so old and healthy at the same time, the researchers found, was because of the absence of dangerous mutations. Apparently, van Andel-Schipper had a superior system for repairing or aborting cells with dangerous mutations, and this did wonders for her life.

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So, what can we learn from all of this? Well, first of all the study’s results imply that it may be feasible to inject patients with stem cells collected earlier life, when these are in abundant supply. These stem cells would be substantially free of mutations and have full-length telomeres. “If I took a sample now and gave it back to myself when I’m older, I would have long telomeres again – although it might only be possible with blood, not other tissues,” she says.

In other words, you’d still look just as old, but feel younger and avoid many complications. Still and idea, but my thought is that some researchers will put this into application soon enough. ZME Science is sure to follow any developments.

Findings were reported in the journal Genome Research.

 

Strands of engineered muscle fiber, stained different colors to observe growth after implantation into a mouse. Duke University

Most advanced lab-grown muscle can self-heal, mouse implant shows

Strands of engineered muscle fiber, stained different colors to observe growth after implantation into a mouse. Duke University

Strands of engineered muscle fiber, stained different colors to observe growth after implantation into a mouse. Duke University

Heralded as one of the biggest advances in the field, scientists at Duke University have engineered muscle tissue that is up to ten times stronger than anything previously achieved. The muscle can contract similarly to native neonatal skeleton muscle and, most importantly, it demonstrates self-healing ability – again, just like the real thing. To demonstrate their work, the researchers also implanted the muscles in bionic mice and followed the muscle fibers as they grew through a window on the back of the living animal.

“The muscle we have made represents an important advance for the field,” said Nenad Bursac, associate professor of biomedical engineering at Duke. “It’s the first time engineered muscle has been created that contracts as strongly as native neonatal skeletal muscle.”

Artificially creating muscles is a great challenge, but if muscle implants are demonstrated in humans, then a slew of injuries or degenerative muscle diseases could be addressed therapeutically. The team led by Bursac found that the two most important aspects that need to be considered when engineering muscles are the contractile muscle fibers and a pool of muscle stem cells, known as satellite cells.

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Self-healing muscle grown in a lab

The latter is of significant important in all muscle carrying organisms. Your muscles has many, many such satellite cells layered around them, waiting in standby until they’re efforts are required. For instance, when an injury occurs to the muscle, like those following a car accident or even a hefty workout, the satellite cells activate and begin the regeneration process.

Destruction and subsequent recovery of engineered muscle fibers that had been exposed to a toxin found in snake venom (credit: Duke University)

Destruction and subsequent recovery of engineered muscle fibers that had been exposed to a toxin found in snake venom (credit: Duke University)

The key to the team’s success was successfully creating the microenvironments—called niches—where these stem cells await their call to duty.

“Simply implanting satellite cells or less-developed muscle doesn’t work as well,” said graduate student Mark Juhas. “The well-developed muscle we made provides niches for satellite cells to live in, and, when needed, to restore the robust musculature and its function.”

First, the researchers ran a series of trials on the muscles in the lab, submitting it to electrical impulses. The muscle contracted showing strength 10 times greater than anything demonstrated in a lab previously. Then, the muscle was damaged using snake venom and satellite cells activated, proving their environment can help the muscle regenerate.

A window peering into progress

Veins slowly growing on implanted muscle in mouse host. Photo: Duke University

Veins slowly growing on implanted muscle in mouse host. Photo: Duke University

Then followed the trial on mice. The researchers inserted their lab-grown muscle into a chamber in the back of mice and implanted a window to follow progress. The evolution turned out to be spectacular, as the muscles proved to grow stronger as the days and weeks passed by. To make things easier, the muscle was genetically engineered to express fluorescent flashes during calcium spikes—which cause muscle to contract.

“We could see and measure in real time how blood vessels grew into the implanted muscle fibers, maturing toward equaling the strength of its native counterpart,” said Juhas.

The ultimate test will follow next, as the researchers need to investigate whether or not the biomimetic muscle can be used to repair actual muscle injuries and disease in humans.

“A number of researchers have ‘grown’ muscles in the laboratory and shown that they can behave in similar ways to that seen in the human body,” said Mark Lewis, an expert in skeletal muscle tissue engineering at Loughborough University, who wasn’t involved in the study. “However, transplantation of these grown muscles into a living creature, which continue to function as if they were native muscle has been taken to the next level by the current work.”

The findings were reported in the journal PNAS.

brown pig

Chimeric organ harvesting: growing human organs inside pigs

brown pig

Photo: freefoto.com

Sure to raise a slew of controversy and debate, researchers in Japan are currently investigating the possibility of growing human organs, like kidneys, livers or even hearts, inside pigs. A real life chimeric tale, as if spawned from the Island of Dr. Moreau. The challenges are numerous though, both technical (we’re talking about growing human organs in a foreign host), legal (human-animal hybrids are illegal in Japan) and of course moral (do we want living, breathing, organ farms – how would it be different from meat farms today?). For now, we can only entertain and ponder these questions, but in Japan things are beginning to shape up towards this goal.

The first steps in this direction were made by Hiroshi Nagashima, a professor at Meiji University, who made chimeric pigs – pigs that contain the genetic signature of two different species. A pilot experiment involved the breeding of what’s called an “a-pancreatic” pig. The genes that code the development of the pancreas in white pigs was switched off, then stem cells from a black pig are introduced into the white pig embryo. When the baby pig is born, it will look like a normal white pig, except it will have a black pig pancreas.

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At Tokyo University, Professor Hiro Nakauchi is taking things further, by using induced pluripotent stem cells (iPS) – adult cell that are culture and hoaxed into behaving like stem cells, without the need to harvest stem cells from embryos. Nakauchi and team cultured iPS cells from brown mice skin cells and introduced these in the embryos of white mice, which similarly to Nagashima’s research had their pancreas development gene turned off. Nakauchi ended up with a white mouse with a brown mouse pancreas. The beauty of iPS cells, however, is that they can be used to develop into any kind of cells, like the constituting tissue that makes up organs. This is the basis for growing human organs in the lab, something that is currently in development with mixed results.

Man and beast

The Japanese researchers hope they can ultimately grow a human organ inside a pig host, or maybe some other surrogate animal model for that matter. If successful, the human organ grown would theoretically be identical to the human organ needing replacement, since it would have been grown from the patient’s iPS cells. The medical implications would be outstanding. Millions of people all over the world require an organ transplant of some kind and for many the waiting list is too long for survival.  Organs grown this way would actually be ideal, since there wouldn’t be a case of biological incompatibility anymore.

Is such a thing possible in the first place?

Black pig pancreas in a white pig host. Brown mouse pancreas in a white mouse host. Human pancreas inside a pig. Obviously, the latter case doesn’t follow the same pattern. We’re talking about extremely distant species. With confidence, however,  Prof Nakauchi  claims it can be done. In Japan human-animal hybrids are illegal and if any of his research can go further, the laws need to be changed. If not, Nakauchi can always move his research to a more permissive country.

Footage from the movie "The Island of Dr. Moreau".

Footage from the movie “The Island of Dr. Moreau”.

Then there’s another concern. In HG Wells’ sci-fi classic, The Island of Dr Moreau, an oddball scientists breeds all sort of chimeric creatures – grotesque beings that are horse, dog and pig at the same time (M’ling). Nakauchi assures that the genetically engineered pigs would still be pigs, it’s just that they’d be carrying human tissue. Anticipating controversy, the Japanese scientist points to In Vitro Fertilisation (IVF) which was invented in Britain in the 1970’s and which at the time sparked a lot of debate. Today, IVF is no longer seen as strange or unethical and in time Nakauchi’s research may also become accepted if the results measure up, he says.

 

(C) Nature Biotechnology

First functioning lung and airway cells grown from human stem cells

Biotechnology is growing fast and the findings researchers are making the field are nothing short of breathtaking. Previously, ZME Science reported in the past few years alone a series of milestone premiers: the first bioengineered kidney and 3-D human kidney cells, the  first functioning blood vessels, the first teeth-like structures, a bioengineered heart that beats on its own and many more. All of these vital tissue and precursor organs were grown in the lab using stem cells or induced pluripotent stem cells. Now, yet another milestone confirms the growing trend after researchers at Columbia University Medical Center reported they’ve created functioning lung and airway cells.

(C) Nature Biotechnology

(C) Nature Biotechnology

Lung transplants are among the most complicated medical procedures, and patients have one of the poorest prognosis post-transplant. This is because it’s very difficult to find biocompatible lungs for transplant. Growing new lungs in the lab directly from patients’ cells, however, offers a massive workaround. More or less, the resulting lung would be very similar to the one the patient loses during transplant, greatly reducing the chance the immune system will reject the lung. Growing organs may seem like SciFi and although we’re still far away from seeing a fully fledged, lab-grown organ becoming successfully transplanted, we’re getting there.

“Now, we are finally able to make lung and airway cells,” study leader Dr. Hans-Willem Snoeck, a professor of microbiology and immunology at Columbia University in New York, said in a statement.

A breath of fresh air

Previously, Snoeck and team discovered a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells (adult skin cells that have been reprogrammed into stem cells) into anterior foregut endoderm – precursors of lung and airway cells.  Now, the same researchers have found a set of chemicals that coax stem cells in growing into epithelial cells which coat the surface of lungs.

In fact, resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. The kind of cells are vital because they produce  surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

 “Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplants — that is, transplants that use a patient’s own skin cells to generate functional lung tissue,” said the authors of the paper published in the journal Nature Biotechnology.

Transplants may be long away, but lab-grown lungs from diseased patients could serve a much more immediate purpose in the future. Early-stage precursor lungs could become highly valuable in research, where they could act as biological test beds for various types of drugs or kinds of treatment. This applies for virtually any kind of organ. Even in this primitive stage, testing could be made. For instance, idiopathic pulmonary fibrosis (IPF) is a lung disease  in which type 2 alveolar epithelial cells are thought to play a central role.

“No one knows what causes the disease, and there’s no way to treat it,” says Dr. Snoeck. “Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures.”

“In the longer term, we hope to use this technology to make an autologous lung graft,” Dr. Snoeck said. “This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient. In this way, rejection problems could be avoided.” Dr. Snoeck is investigating this approach in collaboration with researchers in the Columbia University Department of Biomedical Engineering.

“I am excited about this collaboration with Hans Snoeck, integrating stem cell science with bioengineering in the search for new treatments for lung disease,” said Gordana Vunjak-Novakovic, PhD, co-author of the paper and Mikati Foundation Professor of Biomedical Engineering at Columbia’s Engineering School and professor of medical sciences at Columbia University College of Physicians and Surgeons.