Functioning Kidney Tissue Produced from Stem Cells

For the first time in the history of medical science, scientists from the University of Manchester have been able to produce functioning human kidney tissue inside a living organism. For the medical community and for ailing patients, this means more effective treatments for kidney disease.

The study, which was published in the journal Stem Cell Reports, was led by Professors and researchers Sue Kimber and Adrian Wolf.

The team were able to grow kidney glomeruli from embryonic stem cells in a laboratory. Kidney glomeruli serve an important function in the filtration of blood and subsequent production of urine. In fact, these microscopic parts of the kidney serve within a network as the first stage in the filtering process. These tiny capillaries grew inside of a plastic culture dish containing a nutrient broth full of molecules to promote kidney development.

Once the kidney glomeruli grew and matured, they were combined with what researchers are calling ‘a gel like substance’. It acted as natural connective tissue which formed a tiny clump and was injected into mice.

The result: mini, human-like kidneys.

Three months after the initial injection, the structures that actually produce urine as a process of removing waste from the blood had formed. The structures, called nephrons, contained most of the parts present in human nephrons and tiny human blood vessels had formed which were nourishing the new kidney structures. But, these new kidneys aren’t yet fully functioning. They lack an essential artery that pumps more blood into them.

Nonetheless, the system was successfully filtering, producing and excreting urine.

“We have proved beyond any doubt these structures function as kidney cells by filtering blood and producing urine – though we can’t yet say what percentage of function exists,” said Professor Kimber.

It’s a stunning advancement in biological and medical science but there is still a ways to go before scientists will be able to grow functioning kidneys to replace failing kidneys in patients. Where human kidneys have about one million glomeruli in their kidneys, this mouse-grown structure contained only a few hundred.

The study was supported by The University of Manchester’s School of Biological Sciences, Manchester Regenerative Medicine Network (MaRM) and Kidneys for Life and funded by The Medical Research Council and Kidney Research UK. It’s clear why: There are over 100,000 people on the kidney transplant waiting list. The waiting list has doubled in size over the last 10 years and people are waiting 5-10 years for a transplant. While hundreds of thousands of people are organ donors, less than 1 percent of deaths offer organs that can be used.

But it’s not just people on transplant waiting lists that are suffering. When you include dialysis, the number grows exponentially.

“Worldwide, 2 million people are being treated with dialysis or transplantation for kidney failure, and sadly another 2 million die each year, unable to access these treatments,” Woolf said in a press release.

With such a growing need for kidneys and very limited availability, it’s paramount that scientists work to find an alternative. This is a great first step and could potentially save the lives of millions.

“… We are tremendously excited by this discovery — we feel it is a big research milestone which may one day help patients,” Woolf said.

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Stem Cells Capable of Regenerating Lung Tissue

Over the last several months, studies and trials from around the world have found new and groundbreaking ways to repair lung functions in both humans and mice. In the latest study, researchers from the Perelman School of Medicine at the University of Pennsylvania report identifying a lung stem cell that repairs the organ’s gas exchange compartment.

The findings will be essential in repairing slow to regenerate lung tissue that has been damaged by respiratory ailments like severe influenza, pneumonia, cystic fibrosis and bronchitis to name a few. The European Respiratory Society reports that an estimated one billion people are currently suffering from chronic respiratory conditions.

The team – led by Edward E. Morrisey, PhD, a professor of Cell and Developmental Biology, director of the Penn Center for Pulmonary Biology and scientific director of the Institute for Regenerative Medicine – published their findings in February in Nature.

The lung is often considered one of the most complex organs and in order to find treatments, the team first had to seek to understand its function and complex structure.

“One of the most important places to better understand lung regeneration is in the alveoli, the tiny niches within the lung where oxygen is taken up by the blood and carbon dioxide is exhaled,” Morrisey said. “To better understand these delicate structures, we have been mapping the different types of cells within the alveoli. Understanding cell-cell interactions should help us discover new players and molecular pathways to target for future therapies.”

One of the cell types that line the alveoli are called epithelial cells which are vital in regenerating damaged tissue and restoring gas exchange (breathing) after an injury or illness. Organs like the intestine turn over the entire epithelial lining every five days. But, like we’ve said, lung tissue is slow to regenerate.

In studying epithelial cells in general, the team found and studied an alveolar epithelial progenitor (AEP) lineage which acts as a wetting agent and keeps the lungs from collapsing.

By studying mouse AEPs, the team was able to identify a conserved cell surface protein called TM4SF1. TM4SF1 was used to isolate AEPs from the human lungs which were then used to generate three-dimensional lung organoids.

“From our organoid culture system, we were able to show that AEPs are an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies,” Morrisey said.

These studies, while in their beginning stages, provide much-needed insight into how the lung regenerates. By exploring molecular pathways, they may be able to promote AEP function, design drugs that activate signaling within the lung and promote lung regeneration.

“We are very excited at this novel finding,” said James P. Kiley, PhD, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, which supported the study.

“Basic studies are fundamental stepping stones to advance our understanding of lung regeneration. Furthermore, the NHLBI support of investigators from basic to translational science helps promote collaborations that bring the field closer to regenerative strategies for both acute and chronic lung diseases.”

With access to more than 300 lungs through the lung transplant program, the team plans to dive deeper into their understanding of influenza-damaged lung tissue in particular. Such research naturally lends itself to the understanding of other respiratory ailments and has the potential to save the lives of thousands around the world.

Struggling With Menopause? New Stem Cell Treatments Can Help

After stem cells from bone marrow were injected into the ovaries of 33 women, the scientific community is hopeful that the new treatment may be able to help reverse the effects of early menopause and even allow women to continue having children naturally. The trial focused on women with premature ovarian failure (POF) and after just six months of treatment, they began having periods again.

To understand the far-reaching effects of the new treatment, we must first understand the extent to which menopause and POF can affect women.

When occurring after the age of 40, menopause is a normal condition. It marks the end of a woman’s reproductive years as her body stops releasing an egg every month. Unfortunately, while natural, it can induce several uncomfortable changes in the body including slowed metabolism, weight gain, mood changes, hot flashes, thinning hair and dry skin.

When menopause occurs before the age of 40, it’s considered premature ovarian failure (also known as primary ovarian insufficiency). Women affected by POF can become infertile and develop dementia, depression, anxiety, heart disease and osteoporosis.

Until now, there were no fertility treatments that could help the 1 in every 100 women suffering with POF. Some doctors prescribe hormonal replacements to treat other symptoms of POF but even then, their chances of having children are reduced by half and the injection regimes are difficult to keep up with. Other women seek egg donors but, because of religious, cultural, ethnic, or monetary reasons, many women aren’t able to.

The aim of the pioneering stem cell research by US scientists was to ‘‘support improvement in quality of life and reverse infertility’ and so far, it looks like they’ve done just that. Their findings were presented at the Society of Reproductive Investigation in San Diego, California in early March and while the study is ongoing, the results are cause for celebration.

Women who received stem cell injections experienced increased oestrogen levels, symptoms from hot flashes and insomnia decreased, and after six months, their periods began again. What’s more, no complications or safety issues have been reported making it an extremely viable option for women going forward.

Dr Kate Maclaran and Dr Marie Gerval of the Daisy Network charity agree, saying: ‘This study offers hope for women with POI that in the future, they may be able to conceive naturally or have fertility treatment using their own eggs.’

Dr Christos Coutifaris, president of the American Society for Reproductive Medicine (who was not involved in the study) shares the optimism of those who were involved, saying ‘‘These preliminary findings are exciting. If these observations are validated under further experimental protocols, their implications for female fertility and reproductive hormonal function may prove extremely significant.’

Through the injection of stem cells derived from bone marrow, ovarian function can be stimulated, allowing the return of ovulation and normal hormone levels as well as the possibility of pregnancy. All of the women in the study are currently trying to get pregnant and, once the research has been fully carried out, the option to use stem cell therapy as a treatment for infertility across the board will be explored.

This isn’t the first study exploring the use of stem cells in treating infertility. Back in 2009, scientists in China showed that is was possible to isolate stem cells in mice, store them, and then transplant them back into sterile females to enable them to give birth. But, in this most recent study from US researchers, patients are able to reactivate their own ovaries.

The scientific community and women everywhere are looking forward to final results from the study which will show if the women will, in fact, get pregnant as a result of stem cell injections.

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.

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.

FDA Approves Mayo Clinic’s Automated Bioreactor

The Food and Drug Administration (FDA) has approved a new platform developed by the Mayo Clinic’s Center for Regenerative Medicine that can mass produce stem cells in a way never done before. This is one of the first automated methods approved in the United States. Before this momentous approval, patient’s had to wait sometimes months for medical treatment that involved the creation of multiple stem cells. Now, stem cells are being manufactured in the billions in just a few days.

To understand the far-reaching effects of the FDA’s approval of the Mayo Clinic’s automated bioreactor, we must first look to understand the history of stem cell research and production.

Stem cells are – essentially – shape-shifters. They can develop and differentiate into other cells and repair and regenerate damaged tissue. Because of this, scientists and researchers are looking to stem cells to help treat a variety of conditions, from Parkinson’s and Alzheimer’s diseases, to spinal cord injuries, to Diabetes.

For a long time, the production and harvesting of stems cells has been a very labor-intensive process. Before the automated system, hundreds of hours of around-the-clock work over the course of several months only equated to the cultivation of enough cells for a few patients.

But it’s not just the speed of production that’s revolutionary. Before the Mayo Clinic’s automated bioreactor – which took over four years to develop – scientists needed stem cells from the patients themselves. Now, stem cells from other healthy individuals can be used in treating ailing patients.

“This may make treatments possible in cases where the patient’s own cells are not viable as therapy,” said Abba Zubair, M.D., Ph.D., medical director of Transfusion Medicine and the Human Cell Therapy Laboratory on the Florida campus. “In addition, because the cells can be produced in days instead of months, it may also make treatments available on short notice when they’re needed for acute care.”

The Mayo Clinic – a non-profit organization out of Jacksonville, Florida – was founded in 1889 and since then has been dedicated to finding solutions to transform medicine and surgery. With the automated bioreactor, they’ve succeeded in doing just that. So far, the scope of possibilities for stem cell research is limitless as it’s not just current patients that could benefit from the recent development. Given that stem cells can now be produced in the billions, they can rigorously test other possible treatments using stem cells.

“Although Mayo Clinic has been poised to scale up regenerative clinical trials, to date we did not have the capacity to support them. With this new technology, we now can develop phase II trials enrolling larger numbers of patients to fully test the efficacy of cell-based therapies, ” said Zubair.

They plan to use this new stem cell platform to advance therapies in degenerative diseases that, as of yet, have no cure.

Stems cells have already been proven to be vital in repairing tissue, skin, and bone. With the new, more efficient technology, the Mayo Clinic is looking to study and treat diseases like Arthritis that currently affects over 350 million people worldwide.