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.

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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.

Could Stem Cells Repair Loss of Smell?

A gradual loss or impairment of our sense of smell is a natural part of the normal ageing process. As we get older, many of us will experience a decline in our olfactory function, this will often result in a compromised or complete loss of smell. This in turn, affects the sense of taste. Loss of either, or both of these senses can significantly impact quality of life, and be hazardous to health and nutritional status.

This loss of smell is largely caused by a slow loss of stem cells in the nasal tissue that are present in young people, but lessen in number with age.

To date there have been no treatment options available to repair a person’s sense of smell.

Now, researchers at Tufts University School of Medicine in Boston are investigating the behaviour of stem cells related to the sense of smell in older people. Their research could be a step in the right direction to preventing deterioration and loss of smell in the future.

Regenerating nasal tissue

The research, led by Dr. James E. Schwob, managed to provide the first evidence that it is possible to regenerate nasal tissue in mice, therefore enlarging the population of adult stem cells.

Past research has shown that stem cells might regenerate in response to injury as part of the natural healing process. Dr, Schwob and his team tested this theory on mice and found that human stem cells regenerated in mice with injured nasal tissue. Perhaps more encouragingly, when they were transplanted into other mice, they were able to regenerate into different cell types.

Similarities can be seen between this study, and the Nobel Prize-winning approach developed by Dr. Shinya Yamanaka. Unlike Yamanaka, who induced cells taken from adult tissues to behave like embryonic stem cells by forcing them to express four genes, Schwob’s approach determined that only two of these four factors were critical to transforming the olfactory cells.

“The direct restoration of adult stem cells has implications for many types of tissue degeneration associated with aging, though we are several years away from designing actual therapies based on this work. The olfactory epithelium is a singularly powerful model for understanding how tissues regenerate or fail to do so,”

said Jim Schwob, M.D./Ph.D., a professor of Developmental, Molecular & Chemical Biology at Tufts University and senior author of the study.

If we can restore the population of stem cells in the olfactory epithelium by regenerating them or by administering the right drug as a nasal spray, we may be able to prevent deterioration in the sense of smell,” he continued.

Stem Cell Research Holds Possibilities for Diabetic Foot Ulcers

Scientists in Glasgow have made a breakthrough, which could make a big difference to sufferers of diabetes by helping to treat their foot ulcers.

Foot ulcers are a common side effect of diabetes caused by nerve and blood vessel damage. An estimated 15% of diabetes patients develop foot ulcers as a result of the condition.

The impact of foot ulcers can be severe – for some patients the severity of the ulcers eventually leads to amputation.

Hope for Treatment

This latest study carried out by researchers at the Glasgow Caledonian University has managed to reprogramme human cells using leftover skin tissue from surgery to replicate wounds from diabetic foot ulcers.

The team used donor skin tissue samples from people with type 2 diabetes. From these they created batches of human stem cells ready to be reprogrammed into different types of cells including brain and nerve cells. It is hoped that in the future these cells will be able to be used to repair tissue and skin damage resulting from foot ulcers, and hopefully prevent the need for amputation.

The research is part of a three-year project funded by Animal Free Research UK who is hoping to develop new treatments for foot ulcers that do not need to be tested on animals, as currently is the case.

Professor Ann Graham, lead author of the study said:

“Over 135 diabetes-related amputations are carried out each week in the UK. We know that this is a growing problem and we hope that our work can inform research and aid others who require access to human material for medical research.”

Future research by the team will examine the links between type 2 diabetes and Alzheimer’s disease, as well as diabetic wound healing and psoriasis.

Regenerative Medicine Market projected to reach $5.5 Billion

According to analysis found in a new report, “Regenerative Medicine Market, 2014 – 2025”, the global regenerative medicine market size is expected to reach USD 5.59 billion in just eight years.

This high rate of growth is being attributed in part to the increased global geriatric age, with the World Health Organization now revealing the average life expectancy to be 71.4 years (2015). This is in addition to the increased prevalence of Neurodegenerative disorders, along with Orthopedic and other aging-related disorders. As biotechnology has advanced to seek treatments for these and other illnesses, this has lead to increased investment in the field. The biotechnology has so far enabled scientists to garner more in-depth knowledge of cell division, differentiation and mutation, as well as cell metabolism. According to a press release from Research and Markets, “this enriched knowledge, coupled with emergence of novel streams of biotechnology such as gene therapy and nanotechnology, further prospered use of cell-based technology in therapeutic treatment.”

Advancements have been made thanks to the identification of ways to use stem cells in regenerative medicine, according to the report. There has been increased coverage of such trials, and so many regenerative experts have looked to other potential fields for similar applications, such as induced pluripotent stem cells (iPSC). According to the report, the demand for global regenerative medicine exceeded USD 1.7 billion in 2016, a figure that is expected to rapidly rise over the coming years as this research has lead to a strong pipeline of potential products and treatments. The study reveals that in  2016, therapeutics emerged as the largest product segment in the market, owing to it’s high rate of usage and  implementation. Where global regenerative services are concerned, demand for facilities such as tissue banks and cellular engineering tools is “expected to drive demand in the segment”.

Another key finding in the report was the impact that the emergence of gene therapy techniques has had on the industry. This has been a major driver, as treatments “Regenerative medicine grabs the attention of the healthcare industry owing to its promising applications along with significant advances in supportive fields including tissue engineering, stem cells, gene therapy, drug discovery and nanotechnology,” reads a report summary. “For instance, 3D printing over scaffold with stem cells to restore structure as well as functional characteristics of biological cells, tissues, and organs.Biologics, individually or in combination with cells or devices, are explored to support regenerate the biological functions of cells, tissues, or organs. A number of combinatorial therapies to support chemotherapy and other cancer treatments by prevention as well as treatment for cancer relapse are in development phases. In addition, rising prevalence of complicated degenerative disorders such as age-related macular degeneration, Alzheimer’s disease, and Parkinson’s disease, especially in the aging population resulted in high investments in R&D to develop therapeutic solutions.”