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.

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.

Biomarker predicts risk of breast cancer recurrence after tamoxifen treatment

See on Scoop.itInteresting Innovation

A biomarker reflecting expression levels of two genes in tumor tissue may be able to predict which women treated for estrogen-receptor-positive breast cancer should receive a second estrogen-blocking medication after completing tamoxifen treatment.

See on www.sciencedaily.com