New Trial Suggests Stem Cells Could Heal Patients’ Brains Post-Stroke

Thanks to researchers from the University of Georgia’s Regenerative Bioscience Center and startup ArunA Biomedical, stroke victims have a renewed sense of optimism when it comes to one day fully recovering. The new treatment, called AB126, uses stem cells to decrease brain damage and increase the brain’s natural healing tendencies. As of late-February, clinical trials have proven effective on both mice and pigs. Scientists are now looking to begin tests on humans in 2019.

The treatment will mean a second chance for hundreds of thousands of people. According to the Stroke Association, one person suffers from a stroke every two seconds and strokes are the fourth leading cause of death in the UK. Before we understand the future of treatment, we must first look to understand why strokes occur.

Ischaemic strokes – which account for 85 percent of all strokes – are caused by a blockage that cuts off blood supply to the brain. Haemorrhagic strokes – which account for the other 15 percent of all strokes – are caused by blood vessels bursting within or on the surface of the brain. In either case, because the brain is affected, the whole body bears the burden. Mobility in both arms and legs is decreased, patients will likely suffer from pain and headaches, and they will also have trouble speaking, understanding, reading, writing, and controlling their bowels.

The consequences of strokes are devastating and far-reaching, impacting nearly every aspect of day-to-day life for survivors. Currently, the best treatment for these victims is tPA (tissue plasminogen activator). This FDA approved IV works by dissolving the blood clot and improving blood flow. While – yes – it has been proven to reverse side effects, it’s only effective if administered within three hours of the stroke. Doctors estimate that only 5 percent of patients are able to make that very limited window.

Unless patients are able to seek treatment within three hours of their stroke, their options are limited to rehabilitation. Recovery depends on the severity of the stroke’s complications.

With AB216, the window is still slightly limited. Researchers are currently administering the treatment no more than 6 days after the patient suffered from the stroke. Of course, this is quite a substantial increase in time from three hours as is the case with tPA.

The study, which was published in the journal Translational Stroke Research, details how extracellular vesicle fluid filled structures called exosomes are used to decrease the amount of brain tissue lost in the injury. These exosomes – which are present in eukaryotic fluids (blood, urine, etc.) – are especially useful in that they can carry multiple doses of treatment and are small enough that they’re able to cross barriers that other cells can’t.

When tested on mice, MRI scans showed close to 35% decrease in size of injury and a 50% decrease reduction in brain tissue loss. This is the first time such results have been seen in exosome stroke treatment studies.

ArunA is already producing AB126 exosomes to meet post-trial demands, with an eye to maintain consistency while still keeping the cost of production low. As apart of their trials, researchers intend to test the effects of the new treatment on traumatic brain and spinal cord injuries as well as epilepsy.

This exciting development is the third in a series that started in 2014 in London. There, researchers from Imperial College Healthcare NHS Trust and Imperial College London, used stem cells from bone marrow in the rapid treatment of strokes. It was the first of its kind published in the UK and the results were encouraging. A particular set of CD34+ stem cells – known to help with the production of blood cells and blood vessels – was used. Four out of five patients were able to live independently six months after suffering a severe stroke that historically leaves only four percent of victims alive.

In 2016, scientists at Stanford University used mesenchymal stem cells, which can mature into multiple types of specialized cells, to restore brain function. The trial involved 18 stroke victims and after depositing the stems cells directly into their brains, one woman made a near full recovery as she regained the function in her legs and learned how to walk again.

Given the progress that has been made over the last several years, stroke victims have a lot to look forward to in 2019 when human trials begin for AB126.

Advertisements

Sheep-Human Hydbrids Pave the Way for Organ Transplants

In late-February, scientists and researchers from Stanford University in California announced that they have successfully grown sheep embryos containing human cells. The announcement came during the annual meeting of the American Association for the Advancement in Austin, Texas and while animal rights activists have raised concerns, the ground-breaking research means that soon, supply for organ transplants might finally meet demand.

The process is called interspecies blastocyst complementation. The approach requires genetically disabling the development of a specific organ in a host embryo and introducing human cells with chimera (animal-human hybrid) formation potential.

Through the research, scientists at Stanford have found that human pluripotent stem cells (hPSCs) can integrate and differentiate in livestock species. The takeaway: soon, transplantable human tissues and organs could potentially be grown in engineered animals. But scientists are quick to say that there isn’t a concrete timeline.

‘It could take five years or it could take 10 years but I think eventually we will be able to do this.’ project lead Dr Hiro Nakuachi, a professor of genetics at Stanford, told the American Association for the Advancement of Science conference.

These findings only represent the beginning of a long road towards meeting this goal. By cell count, only about one in 10,000 cells (or less) in the sheep embryos are human. While it is still 99 percent sheep (and one percent human like you and me), it’s still worth celebrating the successful introduction of human cells.

This isn’t the first experiment of its kind. Back in 2016, researchers from the University of California, Davis successfully combined hPSCs cells with pig DNA inside a pig embryo. Over the course of the 28-day study, the human stem cells showed signs of rooting and growing into a transplantable human pancreas.

Likewise, in 2017, another Stanford team proved that a rat-grown pancreas could successfully be transplanted into a mouse with diabetes. The recipients of the pancreas only needed days of immunosuppressive therapy as opposed to life-long treatment to prevent rejection of the organ and the mice were actually cured of their diabetes.

What’s more, less than two years ago, the US government said it would approve funding on animal-hybrid experiments for the sake of organ transplantation, only to later retract their statement because of complaints from animal rights groups.

While it’s easy to understand arguments from such groups, it’s also important to understand why there is so much interest in chimeras for the sake of organ transplants. It’s possible for organs to grow to adult size within just nine months in these surrogate animals, meaning scientists could have found a much-needed solution for terminally ill patients in need of organs.

“We need to explore all possible alternatives to provide organs to ailing people.” said a member of the team and reproductive biologist Pablo Ross from the University of California, Davis.

In the US, someone is added to the organ donor list once every 10 minutes. There are currently around 76,000 people in the US and 6,500 in the UK on organ transplant lists. 32 people are dying everyday waiting for a transplant. With tens of thousands of people around the world in desperate need, it’s crucial that scientists get the funding they need to find solutions that will save them.

Stem Cell Therapy Becoming More Effective Treatment for Meningitis

Meningitis – a very serious disease if not treated quickly – affects upwards of one million people around the world every year according to the Confederation of Meningitis Organisations. What’s more, it’s difficult to diagnose and it most commonly affects babies, toddlers, children and teenagers.  Current treatments don’t guarantee recovery and the repercussions are life-altering, including late-onset learning difficulties, hearing loss, and general developmental delays. While scientists around the world are working tirelessly to develop and test bone marrow transplants for widespread, life-threatening diseases like cancer, scientists in Germany have been leading the way in allogeneic stem cell transplantation to treat meningitis.

Meningitis can be viral, bacterial or fungal. Bacterial is the most severe. Unfortunately, because it’s so difficult to recognize in its early stages, many children and adults are diagnosed too late and face brain damage and even death. Because common symptoms of meningitis (fever, stiff neck, drowsiness, nausea) resemble common symptoms of dozens of other, less harmful diseases, they might not be taken seriously.

In children, the symptoms are even more difficult to recognize as all signs point to a generally fussy baby rather than a sick one. New mother’s likely won’t rush to hospital because their child is especially irritable, tired, or crying, but all three are known symptoms, specifically in toddlers.

Most often, meningitis is treated one of three ways. In each case, though, doctors will usually start with broad-spectrum antibiotics. They’ll likely even prescribe the antibiotics before the test results come back as a preemptive measure. Patients can also be given a lumbar puncture (spinal tap) as quick and definitive (albeit invasive) alternative to blood tests and x-rays. In a lumbar puncture, cerebrospinal fluid (CSF) is collected and in patients with meningitis, the CSF will show low blood sugar, increased white blood cells, and increased levels of protein.

Patients who are confirmed to have meningitis and who aren’t stabilized with the initial course of antibiotics are often hospitalized and treated with injected antibiotics. But even that isn’t enough often times. In the US alone, 10-15 percent of those diagnosed with meningitis won’t survive and of those that do survive, 10 percent will have lingering symptoms like seizures and stroke.

Doctors in Germany were the first to use allogeneic stem cell transplantation. At a children’s hospital in Halles, Germany, a 19-year old was successfully treated, the infection was controlled, and nearly a full neurological recovery was made. It’s since been dubbed the future of meningitis treatment. In allogeneic stem cell transplantation, stem cells are collected from a matching donor, transplanted into the ailing patient, and the stem cells go to work suppressing the disease and restoring the patient’s immune system. This process is different from autologous stem cell transplants which use the stem cells from the patient’s own body. Allogenic stem cells transplants are used around the world to treat cancers such as lymphoma, myeloma, leukemia as well as other diseases of the bone marrow or immune system.

After the success of the 19-year old in Germany, doctors in Germany are keen to help foreign patients. German Medicine Net, created back in 2001 as an answer to the UK’s waiting list problem, co-operates with renowned institutions for stem cell therapy. Meningitis is regarded as a condition that can be considered for treatment. As research and clinical trials continue, the future of medicine – especially in treating meningitis – truly lies in stem cells.

Stem Cell Research Bringing Doctors Closer than ever to HIV Cure

After 30 years and thanks to extensive stem cell research, scientists are closer than ever before to finding a cure for Human Immunodeficiency Virus, or HIV. Led by Dr. Scott Kitchen, an associate professor of hematology and oncology at UCLA’s David Geffen School of Medicine, the group of US scientists from California, Maine, and Washington have successfully engineered blood-forming stem cells that can carry genes capable of detecting and destroying HIV-infected cells.

But it’s not just that the stem cells were able to destroy the HIV-infected cells, they persisted in doing so for over two years without any negative effects. This equates to long-term immunity and the potential to completely eradicate the disease which, after 1981, quickly became the world’s leading infectious killer.

Kitchen received just over $1.7 million from California’s Stem Cell Agency to carry out his research. California has a special interest in the research as the state ranks second in the United States in cases of HIV. Over 170,000 people are infected, incurring healthcare costs which are being billed to the state. The total has continued to rise and now equates to over $1.8 billion per year.

California’s Stem Cell Agency maintains that “A curative treatment is a high priority. A stem cell based therapy offers promise for this goal, by providing an inexhaustible source of protected, HIV specific immune cells that would provide constant surveillance and potential eradication of the virus in the body.”

In the grant details, Kitchen identifies the potential impact of his research:

“The study will allow a potentially curative treatment for HIV infection, which currently doesn’t exist. This will eliminate the need to administer antiviral medication for a lifetime.”

According to his study published in the journal PLOS Pathogens, Kitchen’s curative treatment involves the use of a ‘optimized’ chimeric antigen receptor (CAR) gene that interferes with interactions between HIV and CD4 cells (white blood cells).When a part of the CAR molecule binds to HIV, it’s instructed to kill the HIV-infected cell. These CAR proteins proved highly effective as they killed HIV-infected cells throughout the lymphoid tissues and gastrointestinal tract, two major sites in HIV replication.

If Kitchen and his team are able to effectively kill off infected cells, they have the potential to save millions of those currently infected with HIV across the globe and can also prevent the virus from advancing into Acquired Immunodeficiency Syndrome, or AIDS. In both cases, the immune system is completely broken down. T-cells, which normally fight and prevent all kinds of bacteria and viruses in the body, are weakened and depleted allowing common and usually treatable infections to become deadly.

Throughout the 80’s and early 90’s, long before stem cell research, the number of people carrying HIV continued to climb as it continued to spread and in 1995, complications from AIDS became the leading cause of death for adults aged 25-44. Shortly thereafter, in 1997, the first truly effective treatment was developed. Highly active antiretroviral therapy (HAART) became the standard and there was a 47% decline in death rates.

By the early 2000’s, the World Health Organization set a goal to treat 3 million people and by 2010 there were 20 different treatment options available.  5.25 million people had treatment and over 1 million more were set to start treatment soon.

While these numbers are a massive improvement and the FDA (Food and Drug Administration) is continuing to approve and regulate HIV medical products, the disease is being slowed rather than halted. According to UNAIDS, over 35 million people are still currently living with HIV/AIDS.

Back in 2011, Kitchen co-authored a study about stem cell research in the treatment of HIV/AIDS in the journal Current Opinion in HIV and AIDS. In it, he said that stem cell-based strategies for treating HIV were “a novel approach toward reconstituting the ravaged immune system with the ultimate aim of clearing the virus from the body.”

Since then, he’s continued to reach higher towards that ultimate aim.

Stem cell treatments utilize patients’ own cells for testing on humans and stem cell advances provide the very necessary opportunity for large clinical trials. It is Kitchen’s hope – and it’s safe to assume the worlds’ hope – that stem cell innovation can one day effectively eliminate the disease, therefore preventing its spread, saving billions of dollars in healthcare costs, and – most importantly – saving lives.

Enhanced Culture System Allows Scientists to Quickly Derive Embryonic Stem Cells From Cows

Ever since embryonic stem (ES) cells were derived from mice in 1981, the scientific community has been looking to do the same with bovine ES cells. Now, 37 years after the cells were cultured from mice and 20 years after the cells were cultured from humans, they’ve finally captured and sustained the cells in their primitive state from a cow. In a study published in the journal Proceedings of the National Academy of Sciences, scientists at the University of California, Davis, detail how they were were able to enhance culture systems and derive stem cells with almost complete accuracy in just 3-4 weeks, a relatively quick turnaround time.

Access to these cells – which are able to develop into more than one mature cell or tissue type from muscle to bone to skin – could mean healthier, more productive livestock and could also give scientists and researchers an opportunity to model human diseases.the

ES cells are easily shaped and moulded and have a potentially unlimited capacity for self-renewal. This means that they’re extremely valuable in regenerative medicine and tissue replacement. In livestock and cattle, they offer the potential to create a sort of Super Cow that produces more milk and better meat, emits less methane, has more muscle, that adapts more easily to a warmer climate, and that is more resistant to diseases.

“In two and a half years, you could have a cow that would have taken you about 25 years to achieve. It will be like the cow of the future. It’s why we’re so excited about this,” author of the study Pablo Ross, an associate professor in the Department of Animal Science at UC Davis’ College of Agricultural and Environmental Sciences, told Science Magazine.

In order to enhance culture systems to sustain the ES cells, scientists at the Salk Institute in San Diego, California, had to expose ES cells to a new culture medium, a substance (sometimes a solid, sometimes a liquid, and sometimes a semi-solid) that’s designed to support the growth of microorganisms and cells. In this case, scientists used a protein to encourage cell growth and another molecule that hinders cells from separating or evolving.

“They used an accelerator and a brake at the same time,” George Seidel, a cattle rancher and a reproductive physiologist at Colorado State University in Fort Collins, told Science Daily.

In order for the enhanced culture systems to eventually lead to genetically superior cows, scientists will first have to augment these ES cells into the cattle’s gametes, or sperm and egg cells. The result would be endless genetic combinations, a sort of controlled evolution and accelerated natural selection. Of course, given that the evolution is taking place in a lab, each ‘generation’ would progress without any animals actually being born.

Ross maintains that “It could accelerate genetic progress by orders of magnitude”.

But it’s not just farmers and consumers that could benefit. The cows’ cells could help create larger models for studying human disease, something that mice simply couldn’t aid in due to their size. The science has also proved effective in deriving and sustaining cells from sheep. On scientists’ radars now: dogs.

Are stem cells the link between bacteria and cancer?

Is there A link between stem cells, bacteria and cancer?

 

Scientists have long believed that an increase in stem cell turnover plays a part in the development of cancer, and now new research has uncovered findings that could strengthen the link.

A study was carried out by the Max Planck Institute in Berlin in conjunction with researchers in Stanford, California, and examined the presence of bacteria and it’s impact on stem cell regeneration. The survival rate for stomach cancer is low, mainly because patients don’t present any symptoms until the cancer has reached an advanced stage. Stomach cancer, or gastric cancer, is caused by the bacterium Helicobacter pylori, which is naturally present in all humans. However, this bacteria acts differently to tumour viruses, leaving scientists in the dark as to how they actually cause cancer. The new research has revealed that this bacterium “sends stem cell renewal in the stomach into overdrive”, a discovery that could open doors to further understanding the cause and therefore treatment of stomach cancer.

About the research

The study confirmed that in the majority of cases, patients with most  stomach cancer experience chronic infections with H. pylori bacterium.

Prof. Dr. Thomas F. Meyer specialises in molecular biology, and worked alongside

fellow researchers at the Max Planck Institute for Infection Biology in Berlin. Having spent many years examining the impact H. pylori has on the stomach’s epithelium cells, the team were in search of answers as to why cancer was able to form in an environment in which cells are being replenished so rapidly. As stem cells are the longest living cells in the stomach, the researchers began their search for answers here. While it had previously been believed that H. pylori affected only the rapidly-replaced surface cells, but the research revealed that the bacteria managed to infiltrate the stem cells, causing them to rapidly multiply.

The team arrived at this conclusion following tracing the behaviour of two different types of stem cells in the stomach of mice. According to Science News Online:

Both respond to a signalling molecule called Wnt, which maintains stem cell turnover in many adult tissues. Crucially, they discovered that myofibroblast cells in the connective tissue layer directly underneath the glands produce a second stem cell driver signal, R-spondin, to which the two stem cell populations responded differently. It is this signal, which turned out to control the response to H. pylori: Following infection, the signal is ramped up, silencing the more slowly cycling stem cell population and putting the faster cycling stem cell population into overdrive.

According to one of the study authors and clinical scientist Michael Sigal, these results substantiate the theory that chronic bacterial infections are strongly linked with cases of stomach. “Our findings show that an infectious bacterium can increase stem cell turnover,” he says. “Since H. pylori causes lifelong infections, the constant increase in stem cell divisions may be enough to explain the increased risk of carcinogenesis observed.”

Could Stem Cells Be Used To Restore Vision?

The eye is one of the most structurally complex parts of the body. Different disorders of the eye develop when one or more of the components stop working. This is why it is so difficult to treat conditions of the eye, and reverse sight loss.

Stem cells may well hold the answer.  By replacing damaged cells with new, healthy, specialised cells, it could be possible to reverse the damage done and restore vision.

Currently the only clinically approved stem cell treatment for the eye is Holoclar®, a treatment which restores vision to patients with damaged corneas by transplanting limbal stem cells into areas where these cells are lacking.

Use in Macular Degeneration

One of the leading causes of vision loss is Macular Degeneration (MD), a painless, age-related eye condition, which causes the person to lose their central vision making vision blurry.

Stem cell therapy has been trialled to treat MD but has so far been unsuccessful due to the replacement cells struggling to integrate into the original tissue.

Researchers may have found a solution to this in the form of an injection of an  immune system protein- Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) – to assist with the integration.  Research carried out by the Buck Institute showed success in retinal stem cell transplants on congenitally blind mice, and human trials are the next step.

If the protein is successful in human therapy, it could be used to treat early-stage MD in the future.

MANF has previously been studied by other scientists, including  Ajan Rejinald, CEO of Celixir,  for its role in conditions like Parkinson’s disease