Stem Cell Clinic

Engineering thyroid cells from stem cells may lead to new therapies – Medical News Today

Scientists have found a way to efficiently engineer new thyroid cells from stem cells. The discovery, performed in mice, is the first step toward engineering new human thyroid cells in order to better study and treat thyroid diseases.

A report on the work - led by Boston University School of Medicine (BUSM) in Massachusetts - is published in the journal Stem Cell Reports.

The thyroid is a gland in the middle of the lower neck. Although only small, it produces hormones that reach every cell, organ, and tissue to help control metabolism - the rate at which the body makes energy from nutrients and oxygen.

Thyroid diseases are common conditions in which the gland is either overactive and produces too much hormone (hyperthyroidism), or underactive and produces too little (hypothyroidism).

It is thought that around 20 million people in the United States are living with some form of thyroid disease, the causes of which are largely unknown.

Most thyroid disorders are chronic or life-long conditions that can be managed with medical attention. However, approximately 60 percent of cases are undiagnosed.

Undiagnosed thyroid diseases can lead to serious conditions, such as cardiovascular diseases, infertility, and osteoporosis.

Stem cells are cells that have the potential to mature into many different cell types. Particular patterns of genetic switches and signals direct the maturing stem cells toward their individual fates.

Fast facts about hyperthyroidism

Learn more about hyperthyroidism

In their study, the researchers found a way to coax genetically modified embryonic stem cells from mice to develop into thyroid cells.

They discovered that there is a "window of opportunity" for doing this efficiently that occurs during cell development.

As they guided the laboratory-cultured embryonic stem cells through various stages of development, the researchers switched a gene called Nkx2-1 on and off for short periods.

They discovered a small timeframe during which the Nkx2-1 gene is switched on that converts the majority of the stem cells into thyroid cells.

Researchers believe that the discovery is the first step toward an effective human stem cell protocol for creating research models and new treatments for thyroid diseases. The principle may also apply to other cell types, they add.

In their paper, they note that stem cells hold great promise as a way to mass produce differentiated cells for research. However, a major roadblock to achieving high yields has been "the poor or variable differentiation efficiency of many differentiation protocols."

"This method resulted in high yield of our target cell type, thyroid cells, but it may be applicable for the derivation of other clinically relevant cell types such as lung cells, insulin-producing cells, liver cells, etc."

Senior author Prof. Laertis Ikonomou, BUSM

Learn how scientists used stem cells to restore testosterone.

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Engineering thyroid cells from stem cells may lead to new therapies - Medical News Today

‘Helper cells’ can turn toxic in brain injury and diseases – Medical … – Medical News Today

For many years, research on neurodegenerative diseases and spinal cord and brain injury has focused on damage to nerve cells, or neurons. Now, a new study of astrocytes - a type of cell that surrounds and supports neurons - finds that there is a subtype that can turn rogue and kill neurons, instead of helping to repair them during injury or disease.

The international study - conducted by a team that includes researchers from Stanford University School of Medicine in California, and the University of Melbourne in Australia - is published in the journal Nature.

The researchers suggest that the findings could lead to new treatments for brain injuries and major neurological disorders such as Alzheimer's and Parkinson's disease.

Lead author Dr. Shane Liddelow, of the department of pharmacology and therapeutics at Melbourne, and the department of neurobiology at Stanford, says that while astrocytes have often been described as "helper" cells, it has also been shown that they can become toxic and contribute to the damage caused by brain injury and disease by killing other brain cells.

"These apparently opposing effects have been a puzzle for some time. By characterizing two types of astrocytes this paper provides some answers to the puzzle," he adds.

For a long time, scientists believed that astrocytes - star-shaped cells in the central nervous system that outnumbers neurons by around five to one - were simply packing cells that provide structural support to neurons.

More recently, it has become clear that astrocytes perform a wide variety of complex and essential roles in the brain and the rest of the central nervous system.

For example, it is now known that astrocytes enhance neuron survival and help to shape brain circuitry.

It is also known that astrocytes can change from benign "resting astrocytes" into "reactive astrocytes" with altered features, following brain trauma, infection, stroke, and disease.

However, what is not so clear is whether reactive astrocytes are good or bad.

In their study paper, the team describes finding a subtype of reactive astrocytes, which they call A1, that occurs in disease and injury.

A1 astrocytes appear to lose the ability to help neurons survive and grow connections. Instead, they induce the death of neurons and oligodendrocytes, the cells that help to grow the myelin sheath that insulates connections between neurons.

In further experiments, the researchers showed that blocking A1 astrocytes stopped them killing neurons.

The researchers also found that A1 astrocytes are abundant in various human neurodegenerative diseases, including: Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

For example, in tissue samples from Alzheimer's patients, they found that nearly 60 percent of the astrocytes in the prefrontal cortex, a region of the brain where the disease causes the most damage, were A1 astrocytes.

Senior author Ben Barres, professor of neurobiology, developmental biology, and neurology and neurological sciences at Stanford, says that their study shows that astrocytes "aren't always the good guys," and concludes that:

"An aberrant version of them turns up in suspicious abundance in all the wrong places in brain tissue samples from patients with brain injuries and major neurological disorders from Alzheimer's and Parkinson's to multiple sclerosis. The implications for treating these diseases are profound."

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'Helper cells' can turn toxic in brain injury and diseases - Medical ... - Medical News Today

Scientists catalogue ‘parts list’ of brain cell types in a major appetite center – Medical Xpress

February 6, 2017 Credit: public domain

Using Harvard-developed technology, scientists at Beth Israel Deaconess Medical Center (BIDMC) have catalogued more than 20,000 brain cells in one region of the mouse hypothalamus. The study, published in Nature Neuroscience, revealed some 50 distinct cell types, including a previously undescribed neuron type that may underlie some of the genetic risk of human obesity. This catalog of cell types marks the first time neuroscientists have established a comprehensive "parts list" for this area of the brain. The new information will allow researchers to establish which cells play what role in this region of the brain.

"A lot of functions have already been mapped to large regions of the brain; for example, we know that the hippocampus is important for memory, and we know the hypothalamus is responsible for basic functions like eating and drinking," said lead author John N. Campbell, PhD, a postdoctoral fellow in the lab of co-corresponding author, Bradford Lowell, MD, PhD. "But we don't know what cell types within those regions are responsible. Now with the leaps we've had in technology, we can profile every gene in tens of thousands of individual cells simultaneously and start to test those cell types one by one to figure out their functional roles."

Each cell in an animal's body carries the same genetic information. Cells take on specific roles by expressing some genes and silencing others. Drop-Seq technology - developed by study co-authors Steven McCarroll, PhD, and Evan Macosko, MD, PhD, both geneticists at Harvard Medical School - makes it possible to assess every gene expressed by individual cells. The automated process means the BIDMC researchers could profile tens of thousands of cells in the same amount of time it once took to profile about a dozen cells by hand.

Campbell and colleagues profiled more than 20,000 adult mouse brain cells in the arcuate hypothalamus (Arc) and the adjoining median eminence (ME) - a region of the brain that controls appetite and other vital functions. The cells' gene expression profiles help scientists determine their functions.

In addition to identifying 50 new cell types, the researchers also profiled the cell types in adult mice under different feeding conditions: eating at will; high-fat diet (energy surplus); and overnight fasting (energy deficit). The technology allowed the researchers to assess how changes in energy status affected gene expression. The cell types and genes that were sensitive to these changes in energy status provide a number of new targets for obesity treatment.

"Sometimes a cell's true identity doesn't come out until you put it through a certain stress," said co-corresponding author, Linus Tsai, MD, PhD, an assistant professor of medicine in the Division of Endocrinology, Diabetes and Metabolism. "In fasting conditions, for example, we can see whether there is further diversity within the cell types based on how they respond to important physiologic states."

Finally, the scientists analyzed previous human genome-wide association studies (GWAS) that revealed gene variants linked to obesity. Noting which brain cell types express such obesity-related genes, the researchers implicated two novel neuron types in the genetic control of body weight.

Campbell and colleagues have posted their massive data set online, making it available to researchers around the world. The open-source information should accelerate the pace of scientific discovery and shape the research questions asked in the field of obesity research.

"The classic way of doing science is to ask questions and test hypotheses," said Lowell, who is a professor of medicine in the Division of Endocrinology, Diabetes and Metabolism. "But the brain is so complex, we don't even know how much we don't know. This information fills in some of the unknowns so we can make new hypotheses. This work will lead to many discoveries that, without these data, people would never have even known to ask the question."

Explore further: Using genes to understand the brain's building blocks

More information: A molecular census of arcuate hypothalamus and median eminence cell types, Nature Neuroscience, nature.com/articles/doi:10.1038/nn.4495

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Using Harvard-developed technology, scientists at Beth Israel Deaconess Medical Center (BIDMC) have catalogued more than 20,000 brain cells in one region of the mouse hypothalamus. The study, published in Nature Neuroscience, ...

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Scientists catalogue 'parts list' of brain cell types in a major appetite center - Medical Xpress

Reprogrammed skin cells shrink brain tumors in mice | Science | AAAS – Science Magazine

Mouse and human skin cells can be reprogrammed to hunt down tumors and deliver anticancer therapies.

Imagine cells that can move through your brain, hunting down cancer and destroying it before they themselves disappear without a trace. Scientists have just achieved that in mice, creating personalized tumor-homing cells from adult skin cells that can shrink brain tumors to 2% to 5% of their original size. Althoughthe strategy has yet to be fully tested in people, the new method could one day give doctors a quick way to develop a custom treatment for aggressive cancers like glioblastoma, which kills most human patients in 1215 months. It only took 4 days to create the tumor-homing cells for the mice.

Glioblastomas are nasty: They spread roots and tendrils of cancerous cells through the brain, making them impossible to remove surgically. They, and other cancers, also exude a chemical signal that attracts stem cellsspecialized cells that can produce multiple cell types in the body. Scientists think stem cells might detect tumors as a wound that needs healing and migrate to help fix the damage. But that gives scientists a secret weaponif they can harness stem cells natural ability to home toward tumor cells, the stem cells could be manipulated to deliver cancer-killing drugs precisely where they are needed.

Other research has already exploited this methodusing neural stem cellswhich give rise to neurons and other brain cellsto hunt down brain cancer in mice and deliver tumor-eradicating drugs. But few have tried this in people, in part because getting those neural stem cells is hard, says Shawn Hingtgen, a stem cell biologist at the University of North Carolina inChapel Hill. Right now, there are three main ways. Scientists can either harvest the cells directly from the patient, harvest them from another patient, or they can genetically reprogram adult cells. But harvesting requires invasive surgery, and bestowing stem cell properties on adult cells takes a two-step process that can increase the risk of the final cells becoming cancerous. And using cells from someone other than the cancer patient being treated might trigger an immune response against the foreign cells.

To solve these problems, Hingtgens group wanted to see whetherthey could skip a step in the genetic reprogramming process, which first transforms adult skin cells into standard stem cells and then turns those into neural stem cells. Treating the skin cells with a biochemical cocktail to promote neural stem cell characteristics seemed to do the trick, turning it into a one-step process, he and his colleague report today in Science Translational Medicine.

But the next big question was whether these cells could home in on tumors in lab dishes, and in animals, like neural stem cells. We were really holding our breath, Hingtgen says. The day we saw the cells crawling across the [Petri] dish toward the tumors, we knew we had something special. The tumor-homing cells moved 500 micronsthe same width as five human hairsin 22 hours, and they could burrow into lab-grown glioblastomas. This is a great start, says Frank Marini, a cancer biologist at the Wake Forest Institute forRegenerative Medicine in Winston-Salem, North Carolina,who was not involved with the study. Incredibly quick and relatively efficient.

The team also engineered the cells to deliver common cancer treatments to glioblastomas in mice. Mouse tumors injected directly with the reprogrammed stem cells shrank 20- to 50-fold in 2428 days compared withnontreated mice. In addition, the survival times of treated rodents nearly doubled. In some mice, the scientists removed tumors after they were established, and injected treatment cells into the cavity. Residual tumors, spawned from the remaining cancer cells, were 3.5 times smaller in the treated mice than in untreated mice.

Marini notes that more rigorous testing is needed to demonstrate just how far the tumor-targeting cells can migrate. In a human brain, the cells would need to travel a matter of millimeters or centimeters, up to 20 times farther than the 500 microns tested here, he says. And other researchers question the need to use cells from the patients own skin. An immune response, triggered by foreign neural stem cells, could actually help attack tumors, says Evan Snyder, a stem cell biologist at Sanford Burnham Prebys Medical Discovery Institute in San Diego, California, and one of the early pioneers of the idea of using stem cells to attack tumors.

Hingtgens group is already testing how far their tumor-homing cells can migrate using larger animal models. They are also getting skin cells from glioblastoma patients to make sure the new method works for the people they hope to help, he says. Everything were doing is to get this to the patient as quickly as we can.

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Cellectis gets US go-ahead to test ‘off-the-shelf’ cell therapy – Reuters

Cellectis has won U.S. regulatory approval to run an early clinical trial using its gene edited cell therapy product UCART123 for blood cancers, boosting the French biotech firm's ambitions in the hot area of cancer research.

Following approval from the Food and Drug Administration, Phase I clinical trials will start in the first half of this year, the company said on Monday.

It marks the first time that U.S. regulators have approved clinical testing of an allogeneic, or "off-the-shelf", gene-edited CAR T cell treatment.

The idea of genetically altering immune cells called T cells so that they can attack cancers more effectively has attracted interest from a range of drugmakers.

But while rivals such as Novartis, Juno and Kite have treatments that use modified T cells extracted from individual patients, Cellectis products are derived from healthy donors and aim to be universal.

Its first such "off-the-shelf" cell therapy UCART19, which is being developed with Servier and Pfizer, is now being tested in Phase I trials in Britain for acute lymphoblastic leukaemia and chronic lymphocytic leukaemia.

It has already rescued two babies treated at London's Great Ormond Street Hospital from previously incurable cancer.

UCART123, which is still wholly owned by Cellectis, is designed to help patients with acute myeloid leukaemia and blastic plasmacytoid dendritic cell neoplasm.

(Reporting by Ben Hirschler; Editing by Ruth Pitchford)

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Cellectis gets US go-ahead to test 'off-the-shelf' cell therapy - Reuters

BioTime Acquires Retinal Repair Cell Therapy from UPMC – Genetic Engineering & Biotechnology News

Regenerative medicine company BioTime expanded its ophthalmology portfolio through the acquisition of global rights to the University of Pittsburgh Medical Centers (UPMC) stem cell-derived retinal repair platform IP. The cell therapy technology, developed in partnership with BioTime, generates 3-D retinal tissue from human pluripotent stem cells for use as implants to repair retinas in patients with advanced retinal degradation. The licensing deal has been made through UPMCs Innovation Institute.

We anticipate that this technology, co-developed with the UPMC lab for retinal repair and epigenetics, will allow us to generate three-dimensional laminated human retinal tissue in a controlled manufacturing process," said Michael D. West, Ph.D., co-CEO of BioTime. "This could lead to vision restoration treatments for a variety of blinding retinal degenerative diseases, particularly retinitis pigmentosa, macular degeneration, and diabetic retinopathy, among other diseases and conditions.

BioTime has developed its PureStem pluripotent stem cell technology for generating cell therapies against a range of degenerative diseases. The firms clinical pipeline includes cell therapies for human immunodeficiency virus (HIV)-related lipoatrophy, macular degeneration, leukemia, and spinal cord injury. The lead program, against HIV-related lipatrophy, is undergoing pivotal clinical trials. Preclinical programs are in development against non-small-cell lung cancer and orthopedics. BioTime is separately developing its HyStem hydrogel technology for culturing and delivering therapeutic cells. Its majority-owned OncoCyte subsidiary is leveraging stem cell expertise to develop noninvasive gene expression-based cancer diagnostics.

At the start of 2017, BioTime and its majority-owned subsidiary Cell Cure Neurosciences established a 8600-ft2 cGMP cell therapy manufacturing facility in Jerusalem.

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BioTime Acquires Retinal Repair Cell Therapy from UPMC - Genetic Engineering & Biotechnology News

Trump’s travel restrictions would hurt cell therapy developers says ISCT – BioPharma-Reporter.com

If reinstated, Donald Trumps order restricting travel to the US would hurt the cell therapy sector according to the International Society for Cellular Therapy (ISCT).

US President Donald Trump issued an executive order on January 27 that limited immigration from seven predominantly Muslim countries, halted refugee admission for 120 days, and barred all Syrian refugees.

Last Friday , a judge in Seattle suspended implementation of the order after lawyers representing Washington and Minnesota argued it was unconstitutional and discriminatory.

In response, Trump criticized the presiding judge and vowed to have the order reinstated. However, at the time of writing, nothing has been decided.

If reinstated, the travel restrictions will negatively impact the cell therapy sector according to the International Society for Cellular Therapy (ISCT) a Canada-based group representing doctors, regulators, researchers and industry which raised concerns in a statement today.

The US plays an essential part in cell therapy research as a leading country in the life science industry. It hosts the highest number of international conferences, critical for scientific collaboration and sharing of ideas.

The ISCT also highlighted the leading roles US investors and the FDA play in shaping the global cell therapy sector and warned against any regulations that restrict international collaboration.

ISCT views any policies that would prevent the free movement of properly credentialed scientists, patients, care givers and/or their families from entering the US, as significantly harmful to the sharing of key scientific findings and the ability to deliver cell therapy to all patients.

ISCT President Catherine Bollard told us The Executive Order may result in a loss of talented researchers being able to come and work in the US to develop cell therapeutics given how much the US relies on foreign talent in the research and development sector.

She also suggested that some researchers returning to their country of origin because they do not feel comfortable continuing to live in the US.

Bollard confirmed that ISCT has one member from a country covered by the executive order.

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Trump's travel restrictions would hurt cell therapy developers says ISCT - BioPharma-Reporter.com

Trump’s travel restrictions will hurt cell therapy sector says ISCT – In-PharmaTechnologist.com

If reinstated, Donald Trumps order restricting travel to the US would hurt the cell therapy sector according to the International Society for Cellular Therapy (ISCT).

US President Donald Trump issued an executive order on January 27 that limited immigration from seven predominantly Muslim countries, halted refugee admission for 120 days, and barred all Syrian refugees.

Last Friday , a judge in Seattle suspended implementation of the order after lawyers representing Washington and Minnesota argued it was unconstitutional and discriminatory.

In response, Trump criticized the presiding judge and vowed to have the order reinstated. However, at the time of writing, nothing has been decided.

If reinstated, the travel restrictions will negatively impact the cell therapy sector according to the International Society for Cellular Therapy (ISCT) a Canada-based group representing doctors, regulators, researchers and industry which raised concerns in a statement today.

The US plays an essential part in cell therapy research as a leading country in the life science industry. It hosts the highest number of international conferences, critical for scientific collaboration and sharing of ideas.

The ISCT also highlighted the leading roles US investors and the FDA play in shaping the global cell therapy sector and warned against any regulations that restrict international collaboration.

ISCT views any policies that would prevent the free movement of properly credentialed scientists, patients, care givers and/or their families from entering the US, as significantly harmful to the sharing of key scientific findings and the ability to deliver cell therapy to all patients.

ISCT President Catherine Bollard told us The Executive Order may result in a loss of talented researchers being able to come and work in the US to develop cell therapeutics given how much the US relies on foreign talent in the research and development sector.

She also suggested that some researchers returning to their country of origin because they do not feel comfortable continuing to live in the US.

Bollard confirmed that ISCT has one member from a country covered by the executive order.

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Trump's travel restrictions will hurt cell therapy sector says ISCT - In-PharmaTechnologist.com

British Synbio’s Llama Antibodies recruited for Cancer T-Cell Therapy – Labiotech.eu (blog)

Isogenica has licensed its synthetic llama antibody library to Maverick Therapeutics, which develops cancer T-cell therapies designed to reduce side effects.

Isogenica is a synthetic biology company near Cambridge that develops libraries of therapeutic antibodies. The biotech has granted US-based Maverick Therapeutics licenses to its llamdA VHHantibody library for the discovery, development and commercialization of therapeutic products. In exchange, it will receive upfront, annual and milestone payments as the antibodies are developed by the client.

Isogenicas llamdA VHH library comprisessingle domain llama antibodies created and screened in vitro,which consumes half the time and creates greater diversity than immunizing llamas. According to the company, its llamdA system routinely interrogates the equivalent to the whole antibody repertoire of one million llamas.

Maverick Therapeutics is a very young biotech, spun out from Harpoon Therapeuticsjust last year. The company is backed by MPM Capital, a USVC managed by biotech veteran Patrick Bauerle from Munich.

The company is developing a unique approach to T-cell cancer therapy. Its antibodies are designed to be inactive when administered and only activate in the tumor microenvironment. This way, theT-cells do not attack healthy tissues, avoiding side effects. Japanese big pharma Takeda recently offered the young company 117M ($125M) to develop this technology.

Mavericks approach looks promising since severe side effects are common in T-cell therapies such asCAR-T, with some companies reporting thedeathof several patients. Other companieslike the French Cellectis and Stimunity are also developing their own strategies to increase the safety of CAR-T.

If successful, the development of Isogenicas antibodies by Maverick could bring the British biotech revenues to accelerate the launch of its new library of fully synthetic human antibodies.

Images from Sergey Didenko /Shutterstock

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British Synbio's Llama Antibodies recruited for Cancer T-Cell Therapy - Labiotech.eu (blog)