Stem Cell Clinic

First pain treatment using human stem cells developed – THE WEEK

Scientists have developed the first treatment for pain using human stem cells, which provides lasting relief in mice in a single treatment, without side effects. If the treatment is successful in humans, it could be a major breakthrough in the development of new non-opioid, and non-addictive pain management, the researchers said.

"Nerve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies," said Greg Neely, an associate professor at the University of Sydney in Australia.

"This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain," Neely said in a statement.

The study, published in the journal Pain, used human induced pluripotent stem cells (iPSCs) derived from bone marrow to make pain-killing cells in the lab.

The iPSCs are cells which can develop into many different cell types in the body during early life, and growth.

The researchers then put the cells into the spinal cord of mice with serious neuropathic pain, caused by damage or disease affecting the nervous system.

"Remarkably, the stem-cell neurons promoted lasting pain relief without side effects," said study co-author Leslie Caron.

"It means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting," Caron said.

Because the researchers can pick where to put the pain-killing neurons, they can target only the parts of the body that are in pain.

"This means our approach can have fewer side effects," said John Manion, a PhD student and lead author of research paper.

The stem cells used were derived from adult blood samples, the researchers noted.

Their next step will be to perform extensive safety tests in rodents and pigs.

They will then move to human patients suffering chronic pain within the next five years.

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First pain treatment using human stem cells developed - THE WEEK

Weekly pick of brain tumour research news from around the world – Brain Tumour Research

The first symposium of the South West Brain Tumour Centre was held on Thursday at Derriford Hospital in Plymouth. During a fascinating and very well attended event, topics covered included the mechanism of tumour development, new drug targets, new biomarkers and brain tumour imaging. The South West Brain Tumour centre is of course one of the UK Centres of Excellence funded by Brain Tumour Research.

A really big cancer wide story this week is here Immune discovery 'may treat all cancer' applicable to some solid tumours but not yet brain it really shows the direction of travel toward immunotherapy I have recommended this book before but if interested please do read The Breakthrough by Charles Graeber it is available on Amazon and you can read reviews here - http://www.charlesgraeber.com.Researchers uncover novel drug target for glioblastoma by revealing a cellular pathway that appears to contribute to glioma stem cell spread and proliferation. This pathway shows that glioma stem cells ability to access key nutrients in their surrounding microenvironment is integral for their maintenance and spread. Finding a way to interrupt this feedback loop will be important for treating glioblastoma.

An intelligent molecule could significantly extend the lives of patients with glioblastoma, research finds. The molecule, called ZR2002, which can be administered orally and is capable of penetrating the blood-brain barrier, could delay the multiplication of glioblastoma stem cells resistant to standard treatment. According to scientists in the Metabolic Disorders and Complications Program at the Research Institute of the McGill University Health Centre (RI-MUHC) the ZR2002 molecule is designed to kill two birds with one stone: on top of attacking the tumour, it destroys its defence system.

Researchers find clues to drug resistance in medulloblastoma subtype.US scientists have identified specific types of cells that cause targeted treatment to fail in a subtype of medulloblastoma. They found while the majority of cells responded to treatment, diverse populations within the tumour continue to grow leadingto treatment resistance. They concluded that the diversity of cells within tumours allow them to become rapidly resistant to precisely targeted treatments," and that due to this tumour cell diversity, molecularly precise therapies should be used in combinations to be effective."

Nanoparticles deliver 'suicide gene' therapy to paediatric brain tumours growing in mice So-called "suicide genes" have been studied and used in cancer treatments for more than 25 years. Researchers report here that a type of biodegradable, lab-engineered nanoparticle they fashioned can successfully deliver a ''suicide gene'' to paediatric brain tumour cells implanted in the brains of mice.

According to a study that uncovers an unexpected connection between gliomas and neurodegenerative diseases a protein typically associated with neurodegenerative diseases like Alzheimers might help scientists explore how gliomas become so aggressive. The new study, in mouse models and human brain tumour tissues, was published in Science Translational Medicine and found a significant expression of the protein TAU in glioma cells, especially in those patients with better prognoses. Patients with glioma are given a better prognosis when their tumour expresses a mutation in a gene called isocitrate dehydrogenase 1 (IDH1). In this international collaborative study led by the Instituto de Salud Carlos III-UFIEC in Madrid, Spain, those IDHI mutations stimulated the expression of TAU. Then, the presence of TAU acted as a brake for the formation of new blood vessels, which are necessary for the aggressive behaviour of the tumours.

'Innovative research award' helps Colorado scientists block brain cancer escape routes Cancers used to be defined by where they grow in the body - lung cancer, skin cancer, brain cancer, etc. But work in recent decades has shown that cancers sharing specific genetic changes may have more in common than cancers that happen to grow in an area of the body. For example, lung cancers, skin cancers, and brain cancers may all be caused by mutation in a gene called BRAF. Drugs targeting BRAF have changed the treatment landscape for melanoma, an aggressive form of skin cancer, and are also in use against lung cancers and brain cancers with BRAF mutations. It is really worth clicking through to read more on this and the ultimate goal of identifying new potential targets for combination therapy and new agents that could be added to BRAF inhibiting drugs in brain cancer to keep the cancer from developing resistance.

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Weekly pick of brain tumour research news from around the world - Brain Tumour Research

Researchers uncover link between the nervous system – Tdnews

When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight. In more recent history, John McCain experienced severe injuries as a prisoner of war during the Vietnam War and lost color in his hair.

For a long time, anecdotes have connected stressful experiences with the phenomenon of hair graying. Now, for the first time, Harvard University scientists have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response, which in turn cause permanent damage to pigment-regenerating stem cells in hair follicles.

The study, published in Nature, advances scientists knowledge of how stress can impact the body.

Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair the only tissues we can see from the outside, said senior author Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with and besides, we were genuinely curious to see if stress indeed leads to hair graying.

Narrowing down the culprit

Because stress affects the whole body, researchers first had to narrow down which body system was responsible for connecting stress to hair color. The team first hypothesized that stress causes an immune attack on pigment-producing cells. However, when mice lacking immune cells still showed hair graying, researchers turned to the hormone cortisol. But once more, it was a dead end.

Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role, Hsu said. But surprisingly, when we removed the adrenal gland from the mice so that they couldnt produce cortisol-like hormones, their hair still turned gray under stress.

After systematically eliminating different possibilities, researchers honed in on the sympathetic nerve system, which is responsible for the bodys fight-or-flight response.

Sympathetic nerves branch out into each hair follicle on the skin. The researchers found that stress causes these nerves to release the chemical norepinephrine, which gets taken up by nearby pigment-regenerating stem cells.

Permanent damage

In the hair follicle, certain stem cells act as a reservoir of pigment-producing cells. When hair regenerates, some of the stem cells convert into pigment-producing cells that color the hair.

Researchers found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively. The stem cells all convert into pigment-producing cells, prematurely depleting the reservoir.

When we started to study this, I expected that stress was bad for the body but the detrimental impact of stress that we discovered was beyond what I imagined, Hsu said. After just a few days, all of the pigment-regenerating stem cells were lost. Once theyre gone, you cant regenerate pigment anymore. The damage is permanent.

The finding underscores the negative side effects of an otherwise protective evolutionary response, the researchers said.

Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animals survival. But in this case, acute stress causes permanent depletion of stem cells, said postdoctoral fellow Bing Zhang, the lead author of the study.

Answering a fundamental question

To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed into individual organ systems, cell-to-cell interaction and, eventually, all the way down to molecular dynamics. The process required a variety of research tools along the way, including methods to manipulate organs, nerves, and cell receptors.

To go from the highest level to the smallest detail, we collaborated with many scientists across a wide range of disciplines, using a combination of different approaches to solve a very fundamental biological question, Zhang said.

The collaborators included Isaac Chiu, assistant professor of immunology at Harvard Medical School who studies the interplay between nervous and immune systems.

We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells, Chiu said.

With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying.

The findings can help illuminate the broader effects of stress on various organs and tissues. This understanding will pave the way for new studies that seek to modify or block the damaging effects of stress.

By understanding precisely how stress affects stem cells that regenerate pigment, weve laid the groundwork for understanding how stress affects other tissues and organs in the body, Hsu said. Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area.

The study was supported by the Smith Family Foundation Odyssey Award, the Pew Charitable Trusts, Harvard Stem Cell Institute, Harvard/MIT Basic Neuroscience Grants Program, Harvard FAS and HMS Deans Award, American Cancer Society, NIH, the Charles A. King Trust Postdoctoral Fellowship Program, and an HSCI junior faculty grant.

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Researchers uncover link between the nervous system - Tdnews

Snake Venom Gland Organoids Produce Functional Toxins – The Scientist

Aminiaturized version of the snake venom gland that secretes functionally active toxins can be grown from stem cells, researchers describe January 23 in Cell.

Scientists have previously cultured these simplified tissues, called organoids, from mouse and human stem cells, including minibrains that model neuronal networks, but this study is the first to show that the same techniques work with snake tissue.

Hans Clevers, a principal investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research, and his team used human growth factors to culture the snake venom organoids, reports STAT, but there was one critical difference from mammalian organoids: temperature. The snake organoids needed to be kept a few degrees colder than cultures from mice and humans, Clevers tells STAT, because reptiles are cold-blooded.

The experiment started with three of Cleverss grad students who wondered whether they could grow organoids from other species, reports The Atlantic. They received the egg of a Cape coral cobra (Aspidelaps lubricus) from a breeder and used the labs protocols on mammalian organoids to generate miniature venom glands, which produced the same toxins as that of real snakes. The lab went on to grow organoids from eight other species.

Its a breakthrough, says snake venom toxicologist Jos Mara Gutirrez of the University of Costa Rica in San Jos who was not involved in the study, in remarks to Science. This work opens the possibilities for studying the cellular biology of venom-secreting cells at a very fine level, which has not been possible in the past.

Expanding scientists knowledge of snake venom has important implications for human health. According to the World Health Organization, an estimated 5.4 million people are bitten by snakes every year. Somewhere between 81,000 and 138,000 of those victims die as a result. This neglected public health issue is especially prevalent in Africa, Asia, and Latin America.

The current method of producing antivenom involves injecting a horse with snake venom and collecting the resulting antibodies, a centuries-old technique that requires milking a live snake. Venom gland organoids may be a safer and more economical alternative, reports The Atlantic.

The biotechnology they are describing is a potentially wonderful addition to the toolbox of toxins research generally, writes Leslie Boyer of the University of Arizonas VIPER Institute in an email to STAT. What will future studies reveal about the interaction of components of complex venoms? Can a practical harvest of toxins be generated for cost-effective use in future applications? How do cells full of deadly toxins avoid suicide?

Amy Schleunes is an intern atThe Scientist. Email her ataschleunes@the-scientist.com.

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Snake Venom Gland Organoids Produce Functional Toxins - The Scientist