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A New Drug for ALS, but the Diagnosis Remains Dire – New York Times

By LizaAVILA


New York Times
A New Drug for ALS, but the Diagnosis Remains Dire
New York Times
A.L.S. attacks the nerve cells in the brain and spinal cord that control voluntary muscle movements, like chewing, walking, breathing, swallowing and talking. It is invariably progressive. Lacking nervous system stimulation, the muscles soon begin to ...

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A New Drug for ALS, but the Diagnosis Remains Dire - New York Times

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Do Some Cancer Drugs Offer Hope for ALS Therapy? | ALZFORUM – Alzforum

By JoanneRUSSELL25

26 May 2017

Could tyrosine kinase inhibitors, a standard tool of cancer treatment, help people with amyotrophic lateral sclerosis? Converging evidence suggests that this drug class may slow ALS progression, perhaps through multiple mechanisms. In the May 24 Science Translational Medicine, researchers led by Haruhisa Inoue at Kyoto University, Japan, report that numerous different inhibitors of the tyrosine kinases Src and c-Abl improve the survival of motor neurons from ALS patients. The compounds act by stimulating autophagy, which accelerates the removal of toxic proteins. One of the most potent inhibitors, bosutinib, boosted motor neuron survival by 50 percent and modestly lengthened the lives of ALS model mice, the authorsreport.

In related news, researchers recently reported positive findings from a Phase 3clinical trial of another tyrosine kinase inhibitor, masitinib, at the European Network for the Cure of ALS (ENCALS) annual meeting, held May 18 to 20 in Ljubljana, Slovenia. This inhibitor, which is approved to treat tumors in animals but not people, reportedly doused neuroinflammation in the spinal cord. Patients on the drug maintained motor abilities four months longer than did those on placebo, a statistically significant improvement. AB Science in Paris, the manufacturer, has applied to the European Medicines Agency for approval to use the drug in people, and is planning to start another Phase 3trial this year before applying for approval from the U.S. Food and DrugAdministration.

The data suggest that tyrosine kinase inhibitors might help in other neurodegenerative diseases such as Alzheimers and Parkinsons, which also accumulate toxic proteins and cause neuroinflammation, said Charbel Moussa at Georgetown University, Washington, D.C. He noted that many of these compounds are already FDA-approved for other conditions, and can be used at much lower doses for neurodegenerative disease than for cancer. These drugs represent a promising alternative to antibody and vaccination strategies, he told Alzforum. He was not involved in either of thesestudies.

ALS in a Dish. Stem cells derived from people with familial ALS differentiate into neurons in culture that express motor neuron markers HB9, ChAt, and SMI-32. Nuclei are stained blue. [Courtesy of Science TranslationalMedicine/AAAS.]

The need for new drugs for ALS is immense. In this devastating disease, spinal motor neurons wither, robbing people of motor control and killing them typically within three to five years. Approved treatments are limited to riluzoleand edaravone, which was just approved in the U.S. this month (see May 2017 news). Both modestly slow functional decline, though efficacy data for edavarone remains sparse. Researchers are still seeking betteroptions.

To cast a wider net, Inoue and colleagues screened 1,416 compounds that are either approved for human use or in clinical trials. First author Keiko Imamura generated induced pluripotent stem cells (iPSCs) from a single ALS patient who carried a SOD1 mutation. The authors differentiated these cells into spinal motor neurons and cultured them for seven days, added the compounds, and assessed survival one week later. In this screen, 27 compounds boosted survival more than three standard deviations above that of untreated cells. Half of these compounds targeted the Src/c-Abl signaling pathway. These cytosolic tyrosine kinases participate in numerous cellular processes and are implicated in cancer. To confirm these enzymes mediated the drug effect, the authors knocked down Src and c-Abl with short interfering RNAs, and again saw improved motor neuronsurvival.

Among the hits, the authors selected bosutinib for follow up. This drug is approved to treat chronic myelogenous leukemia, directly inhibits Src and c-Abl, and acts at lower doses than the other compounds in the screen. Bosutinib normalized autophagy in the diseased motor neurons. Compounds that blocked autophagy weakened the protective benefits of bosutinib, suggesting this was its mechanism of action. In keeping with this, other known autophagy boosters, such as rapamycin, also improved motor neuron survival. As might be expected, revving up autophagy cleaned up deposits of misfolded, toxic SOD1. The authors did not detail how inhibition of Src and c-Abl stimulated autophagy, but other work provides clues. Moussa and colleagues have reported that c-Abl inhibition activates the ubiquitin ligase parkin, which then interacts with autophagy proteins such as beclin-1 to stimulate degradation of proteins including A and -synuclein (see Lonskaya et al., 2013; Lonskaya et al., 2014; Wenqiang et al., 2014). A sister compound to bosutinib, nilotinib, is currently in Phase 2 trials for PDand ADthat Moussa and colleagues at Georgetown are running (see Nov 2015 conference news).

Only 2 percent of people with ALS carry SOD1 mutations. What about other forms of the disease? To expand their study, the authors generated motor neurons from three ALS patients with TDP-43 mutations, three with C9ORF72 expansions, and three with sporadic disease. Most people with ALS, regardless of their mutation status, accumulate misfolded TDP-43, and C9ORF72 is the most common familial mutation. In this study, bosutinib lowered levels of misfolded TDP-43 and poly dipeptide repeats formed from the C9ORF72 expansion; it also improved survival in all cell lines save for one from a sporadiccase.

Next, the authors tested bosutinib in the SOD1-G93A mouse model of ALS. These animals become paralyzed at four and die by six months of age. The authors injected a single dose, 5 mg/kg/day, intraperitoneally for six weeks beginning at two months of age. Src and c-Abl activity in the spinal cord was cut in half, indicating target engagement. Treated mice accumulated slightly less misfolded SOD1 and had about three times as many surviving motor neurons in their spinal cords as untreated ones. Nevertheless, treatment delayed disease onset by only 11 days and extended survival by just eightdays.

Why didnt the drug work better in mice, given the promising in vitro data? Nonneuronal cells such as astrocytes contribute to ALS pathology, but Inoues screen did not test for effects of bosutinib on these cells (e.g. Oct 2014 news; Nov 2014 news). In an email to Alzforum, Inoue also suggested that bosutinib could be optimized to better enter the brain and avoid potential off-target effects. Peter Davies at the Feinstein Institute for Medical Research in Manhasset, New York, pointed out that tyrosine kinase inhibitors such as bosutinib are typically not specific for c-Abl. I would like to see pharma make more specific compounds, because then we would learn if the key factor really is c-Abl, rather than another kinase, and there would be fewer off-target effects, Davies wrote to Alzforum. He acknowledged that making specific c-Abl inhibitors is a challenging task, and that companies have tried and abandoned some past efforts for lack ofsuccess.

The findings from bosutinib and nilotinib complement those for masitinib. This veterinary drug seems to act mostly on immune cells. Preclinical studies suggested masitinib inhibits the tyrosine kinases CSF-1R and C-kit in microglia, macrophages, and mast cells, circulating white blood cells that trigger allergic and inflammatory reactions. In animal models, masitinib prevents microgliosis and astrogliosis in the spinal cord, as well as the infiltration of mast cells and macrophages into neuromuscular junctions (see Trias et al., 2016). This provides a rational basis for the protective effects of masitinib in delaying neuromuscular junction denervation. However, more research is needed to understand the detailed mechanism of action of the drug, Luis Barbeito at the Pasteur Institute of Montevideo, Uruguay, wrote to Alzforum. Barbeito presented preclinical data on masitinib atENCALS.

In the Phase 3 trial, 394 patients from nine countries took either 4.5 mg/kg masitinib, 3 mg/kg, or placebo for nearly a year. By prespecified plan, the researchers stratified participants into fast progressors (those who declined more than 1.1 point per month on the revised ALS Functional Rating Scale) and normal progressors. About 85 percent of the participants were normal progressors. Among this group, those taking 4.5 mg/kg masitinib declined 3.4 points less on the ALSFRS-R than the placebo group over the course of the study. This translated to 27 percent less functional decline over this time period, a clinically meaningful difference, according to Jesus Mora at Hospital Carlos III in Madrid, who presented the clinical trial findings at ENCALS. Treated participants maintained greater lung capacity and reported better quality of life than the placebo group. They lasted 20 months before their disease progressed nine points or more on the ALSFRS-R, compared with 16 months for those on placebo. Participants who took the lower 3 mg/kg dose also reported better quality of life, but their trend toward slower functional decline did not reachsignificance.

Other data hinted that the drug was most effective when given at an early stage of disease. When normal and fast progressors were combined, the 4.5 mg/kg dose only slowed decline in those who had had the disease for less than two years. Fast progressors may need earlier treatment, Morasuggested.

The safety profile was acceptable, with no surprises cropping up, the researchers said. The treatment group experienced more serious adverse events than the placebo group. These were scattered across different organ systems and did not fall into any pattern. For oncology use, tyrosine kinase inhibitors are normally given at higher doses, from 6 to 12 mg/kg, with no serious safety issues, the researchers noted.Madolyn BowmanRogers

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Do Some Cancer Drugs Offer Hope for ALS Therapy? | ALZFORUM - Alzforum

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Why Tooth Banking Might Just Be The Next Wave In Stem Cell … – UPROXX

By daniellenierenberg

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Uproxx knows that science, technology, engineering, and math (STEM) disciplines are driving the future of this planet forward. Every day, we see new ideas, fresh innovations, and bold trailblazers in these fields. Follow us this month as we highlight how STEM is shaping the culture of NOW.

Placentas, umbilical cords pretty much anything that comes out of a womans body is awesome in science speak. Stem cells are the master cells of the body, just waiting to help you out when you get sick. Theyre your own personal repair kit, but, like anything, time kind of screws them up. They become damaged or mutated thanks to environmental factors and the aging process and one day, they lose their incredible healing abilities altogether.

The good news is, science has finally tapped into the potential of stem cell research and, in doing so, scientists have found a solution for all that wasted power: babies. Yes, babies are disgusting blobs that poop, eat, and slobber their parents to an early grave, but those little devils also just happen to have a whole army of brand new stem cells still in their original packaging. The key is to get them before they sell out. (Im starting to equate body parts with consumerism and its getting creepy so Ill stop now.)

Placenta blood, placenta tissue, and cord blood are three sources of stem cells doctors are urging new parents to consider saving after the mom gives birth. They provide a range of cool benefits from treating certain forms of cancer to helping people heal from spinal cord injuries and they can be cryogenically frozen to help a body out whenever it needs some extra healing power. And yes, some people do eat them. Google it, there are recipes.

But while the placenta party has been raging for a while now, theres a new method of extracting stem cells that can be done all the way up into a persons teen years, and all it takes is a quick trip to the dentist. Tooth banking has become the latest way people are choosing to cryogenically secure their gene sequence.

In 2013, Songtao Shi, a dentist, was researching regenerative dentistry in a lab when Shi witnessed something extraordinary. He discovered that when you get a cavity, the dentin the inner, hard layer of your tooth that protects the nerve and pulp from exposure builds up. Basically, your tooth tries to protect itself by making more organic matter.

This led Shi to conclude that stem cells did, in fact, exist in teeth. A bit more study found that while stem cells in adult molars were able to create more dentin which is great if you want to re-grow lost teeth instead of paying a fortune for an implant baby teeth, or SHED cells (stem cells from human exfoliated deciduous teeth) contained a whole different set of code.

While cord blood and placenta tissue contain Hematopoietic stem cells which have been used for decades to treat over 80 different diseases, SHED cells contain mesenchymal stem cells which differentiate into nerve cells as well as bone, cartilage, muscle, and fat. Cord blood contains mesenchymal stem cells too, but according to Shis research, SHED cells were able to create something unusual, dentin osteogenic material a material thats not quite dentin, not quite bone but full of possibilities like the ability to reconstruct bone.

Extracting dental stem cells is a complicated and sensitive process. First, the soft tissue has to be extracted, then it has to be disinfected (spoiler alert: your mouth is a cesspool of germs). Scientists then drill through the enamel and dentin to get to the pulp of the tooth where all the stem cells like to hide out. They take the pulp out, digest it with an enzyme, and culture the cells.

Its a lot of work, but the payoff is huge. Even tiny bits of dental pulp can carry hundreds of millions of stem cells.

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StemCyte renewed strategic partnership with the Neonatal Research Institute at Sharp Mary Birch Hospital for Women … – PR Newswire (press release)

By Sykes24Tracey

"The practice of helping babies by providing stem cells at birth has been around for a long time; it makes sense for the sickest infants," said Anup Katheria, MD, director of the Neonatal Research Institute. "We're focused on producing evidence that shows the benefits. We think this could become the foundation for practice-changing birthing techniques, transforming outcomes for the most critical of newborns nationwide."

As a California-based public/private cord blood banking company and with a strong research focus, StemCyte stands ready to help efficiently and effectively to support the partnership with Sharp HealthCare to educate expecting parents of their options, to ensure the information is delivered accurately and consistently, and to collect the cells in cord blood and process and store them with the highest quality standards in the industry.

"We are excited to work with the Sharp Mary Birch Neonatal Research Institute, and we are looking forward to maximizing the capacity for cord-blood banking. Residents of California and people around the world will benefit from the research and increased availability of umbilical cord blood stem cell transplant units." said Jonas C. Wang, Ph.D., CEO/ Chairman of StemCyte Group.

About StemCyte StemCyte's rich history started with a mission of being dedicated to helping the world's physicians save more lives by providing high quality, safe and effective stem cell transplantation and therapy to all patients in need. Located in the US, India and Taiwan, StemCyte has supplied over 2100 cord blood products for over 40 life-threatening diseases to over 300 leading worldwide transplant centers. StemCyte is actively involved in the development of stem cell therapies. StemCyte was the first to donate umbilical cord blood units (UCB) to Dr. Jaing of Chung Gung Memorial Hospital for his clinical trial to use UCB to treat and cure Beta Thalassemia. More excitingly is the work and accomplishments of Prof Wise Young, MD, PhD. Prof. Young has completed Phase II clinical trials on patients with chronic spinal cord injury with UCB and the results are extremely encouraging. StemCyte is chosen by the US Department of Health and Human Services to help establishing a public National Cord Blood Inventory. Its headquarters are located in Baldwin Park, CA. To learn more visit http://www.StemCyte.com.

For more information call 626.646.2500

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/stemcyte-renewed-strategic-partnership-with-the-neonatal-research-institute-at-sharp-mary-birch-hospital-for-women--newborns-300464844.html

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StemCyte renewed strategic partnership with the Neonatal Research Institute at Sharp Mary Birch Hospital for Women ... - PR Newswire (press release)

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Conservative Reps Urge Trump to Fire NIH Head – WMGT – 41 NBC News

By NEVAGiles23


41 NBC News
Conservative Reps Urge Trump to Fire NIH Head - WMGT
41 NBC News
Stem Cell Research.Experimenting with cells in petri dish by adding fluid from a pipette, used in therapeutic cloning, microbiology, genetic engineering an.

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Researchers consider Zika virus for brain cancer treatment – Fox News

By Dr. Matthew Watson

Researchers in the U.K. are set to test whether the Zika virus can fight difficult-to-treat brain cancer by attacking its cells, potentially opening up new pathways to treat the aggressive disease. Researchers will focus on glioblastoma, which is the most common form of brain cancer and has a five-year survival rate of 5 percent, Reuters reported.

QUINOA 'MILK' DIET KILLED BABY, AUTHORITIES SAY

The Zika virus causes severe birth defects in an unborn fetus when contracted during pregnancy by attacking developing stem cells in the brain. However, the disease does not have the same devastating effect on fully developed brains, suggesting that if scientists can harness the virus ability to attack the cancer cells, which are similar to developing brain stem cells, healthy brain tissue will go unharmed.

Were taking a different approach, and want to use these new insights to see if the virus can be unleashed against one of the hardest-to-treat cancers, Harry Bulstrode, a lead researcher at Cambridge University, said, in a statement to Reuters.

ITALY VOTES TO MAKE VACCINES MANDATORY

Researchers will use tumor cells in mice to test the virus, and hope that it will slow tumor growth.

If we can learn lessons from Zikas ability to cross the blood-brain barrier and target brain stem cells selectively, we could be holding the key to future treatments, Bulstrode told Reuters.

Active outbreaks of the mosquito-borne illness were reported in at least 51 countries and territories, with pregnant women advised to avoid travel to so-called virus hotbeds. In addition to birth defects, Zika has been associated with neurological disorders including brain and spinal cord infections. Long-term health consequences remain unclear.

Reuters contributed to this report.

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From hopeless to a miracle: How he got his life back after a crash left him paralyzed – fox6now.com

By Dr. Matthew Watson


fox6now.com
From hopeless to a miracle: How he got his life back after a crash left him paralyzed
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"We came to know he would be a good candidate for this regenerative treatment that we offer, meaning the stem cell injection into the spinal cord. ... "He was only the second to receive the stem cells -- at least that dose he received," added Dr. Kurpad.

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Regenerating medical research payouts? – OCRegister

By daniellenierenberg

In 2004 California ballot measure Proposition 71 was passed, granting $3 billion ($6 billion including interest) in state funds to support politically controversial embryonic stem cell research in California at a time when the federal government was restricting this research. A public agency was established, the California Institute for Regenerative Medicine, to dole out this money across California universities, medical research institutions and biotech companies. During the election campaign, California voters were assured of breakthroughs and cures for conditions like Parkinsons and spinal cord paralysis through celebrity endorsements featuring actors, Nobel prize winners and other notables. Prop. 71 money is dwindling and there is talk about putting a $5 billion renewal initiative on the ballot. So its reasonable to ask what California taxpayers got out of this deal over the past 13 years. Sadly, CIRM hasnt generated a single approved medical treatment. Through September 2016, CIRM has funded only three stem cell research projects that have reached Phase 3 clinical trials (the final step before FDA marketing approval). One of these trials was terminated and the other two are still recruiting patients and are not expected to report out for several years. During the same time, despite embryonic stem cell research restrictions, the federal National Institutes of Health has funded 50 stem cell research projects in Phase 3 trials. The NIH cost per Phase 3 research trial has been five times lower than the state program. Nearly half of the state funding has gone to research infrastructure rather than to actual research.

There also appears to have been blatant conflicts of interest in CIRM research awards. Around 80 percent of CIRM grants have gone to institutions represented on its board of directors. One out of seven CIRM research dollars has gone to Stanford University. One awardee, StemCells Inc., was co-founded by Irving Weissman, Stanfords stem cell program director. StemCells received at least $40 million from CIRM before going belly up. The CIRM board initially turned down a $20 million funding proposal to StemCells, until Bob Klein, the Northern California real estate investor who drafted Prop. 71 and was the first chairman of CIRMs governing board, was reported to have pressured the board to reverse that decision. CIRMs President Alan Trounson abruptly resigned in October 2013, joined the board of StemCells one week later, and then received $435,000 in cash and stocks from them before the company folded last year.

Does it make sense for California taxpayers to fund biotechnology research? Perhaps. A good case can be made that public investments in basic biotechnology infrastructure can have enormous benefits to Californias economy and job growth while generating significant improvements in human health. But public funding should have broader scope and flexibility to go after all promising new technological advances, not just current scientific fads or political controversies. Public funds should be awarded with rigorous oversight and accountability. There should be a sharp line between basic research, which requires public funding and is unlikely to yield short-term tangible cures, despite what celebrity actors say, and getting new medicines to market. Promising new treatments are already well-funded through private venture capital funds and biotech companies, who are much better at picking winners and losers than California taxpayers.

By not providing adequate oversight over potential conflicts of interest and not holding CIRM funding recipients to the same rigorous standards as NIH grant recipients, CIRMs 13 year record of zero new medicines for $6 billion in taxpayer funds is not an experiment that the voters should regenerate at the ballot box.

Joel W. Hay is a professor of Health Economics and Policy at the University of Southern California.

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Repairing and Replacing Damaged Cells – Neuralstem

By raymumme

Neuralstem Cell Therapy:

Different regions of the brain and spinal cord house different, specialized cells. Neuralstem's technology enables the isolation and expansion of human neural stem cells from each of these regions of the developing central nervous system (CNS) in virtually unlimited numbers from a single donated tissue.

The goal of cell therapy is to replace and/or repair dead or diseased cells. Unlike other stem cell technologies, Neuralstem is growing regionally specific cells that are already suited to the task prescribed to them once transplanted into the CNS. In spinal cord indications, for instance, the company will be using human NSI-566 spinal cord stem cells only. Additionally, once inside the body, Neuralstem cells also do not become any cell other than that to which they are fated.

There are two primary ways that these cells can provide therapeutic effects. Create: The transplanted cells may help create new circuitry Express: The transplanted cells may express factors that protect existing cells

We believe that Neuralstem's cells do both.

In preclinical work conducted at major research centers across the U.S., Neuralstem cells integrated and made synaptic contact with the host. The cells also expressed one or more growth factors. These are special chemicals that the CNS uses to operate and thrive. Many of these growth factors are protective of cells. View published papers here: 1, 2, 3.

Neuralstems transplanted cells survive in patients and integrate into the host tissue, creating new circuitry and expressing growth factors. This dual function is important. In spinal cord injury, for instance, the company hopes to create circuitry that will help signals from the brain get to where they need to go. In many indications, the goal is to slow down or halt the degeneration of cells caused by disease, or by injury, by expressing neuroprotective growth factors into the system.

A vital component to the Neuralstem cell therapy platform is the delivery of the cells directly into the gray matter of the spinal cord, where they can protect and integrate with the patient's spinal cord neurons.

Neuralstem's proprietary Spinal Cord Delivery Platform and Floating Cannula were designed specifically by Neuralstem's ALS trial neurosurgeon, Nicholas M. Boulis, MD, for the world's first intraspinal delivery of stem cells. The safety of the device was first reported in data presented at the American Association of Neurologists' 2011 Annual Meeting, and its safety has since been repeatedly validated in the companys completed two ALS clinical studies, in a total of thirty patients, which met primary safety endpoints. In addition to ALS, NSI-566 is also in a Phase I trial in chronic spinal cord injury at UC San Diego School of Medicine. You can view this breakthrough medical device in surgery here.

The Spinal Cord Delivery Platform and Floating Cannula will be utilized to deliver Neuralstem cells in the spinal cord safely and effectively for myriad diseases and injuries. Expected to be the standard in the industry and research community for intraspinal procedures, Neuralstem is licensing the breakthrough cell therapy device to industry and academia.

Delivery of neural stem cells into the brain will be accomplished using well-established stereotactic injection procedures. NSI-566 is in clinical development to treat ischemic stroke utilizing one-time treatments of these intracerebral injections to safely transplant cells near the stroke lesions of ischemic stroke patients.

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Repairing and Replacing Damaged Cells - Neuralstem

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National Multiple Sclerosis Society Commits to $17 Million for 43 Research Projects – Multiple Sclerosis News Today

By LizaAVILA

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National Multiple Sclerosis Society Commits to $17 Million for 43 Research Projects - Multiple Sclerosis News Today

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Motor Neurons Why Are They Important and How Are They Made? – Brain Blogger (blog)

By Dr. Matthew Watson

Motor neurons are the nerve cells in the body responsible for controlling movement. A number of diseases are caused by damage to motor neurons, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In order to treat these diseases, scientists are developing methods to generate new, healthy motor neurons from stem cells. A recent study has elucidated the cellular mechanisms that control the motor neuron differentiation, paving the way for new treatments for motor neuron diseases.

Each time we voluntarily move an arm or leg, or when our lungs involuntarily expand and contract, signals from the brain are sent along a chain to the spinal cord, where motor neuron cell bodies reside. These motor neurons terminate in muscle cells, where they transmit the nerve impulses in order to produce muscle contractions. In ALS, there is a progressive destruction of motor neurons due to either a genetic defect or an unknown environmental trigger. Motor neuron damage in ALS leads to progressive muscle weakness that affects all parts of the body, impairing the ability to speak, swallow, and eventually breathe. SMA is caused by gene mutations and is characterized by similarly progressive damage to motor neurons that causes muscle weakness. If respiratory muscles are affected, SMA can be fatal.

Scientists aim to develop gene therapies for these diseases that can repair the damaged motor neurons and improve the functioning and lifespan of patients. To do this, they must first understand the signals that induce motor neuron development from stem cells. Stem cells are the precursors for every type of cell in the body. They are triggered to differentiate into various cell types via cellular signaling molecules called transcription factors, which act on DNA to turn on specific genes. Which genes are turned on will determine the phenotypic fate of each cell. Typically, each cell goes through several stages of development before reaching its final fate.

A group of researchers from several universities recently teamed up to elucidate these programming pathways. They had previously discovered that a group of transcription factors called the NIL factors Ngn2, Isl1, and Lhx3 can induce motor neuron development from embryonic stem cells without passing through any of the intermediate stages. Moreover, the NIL factors achieved the transition to the motor neuron fate with a 90% success rate, and the process took only two days. This so-called direct programming pathway was an exciting finding with respect to clinical applications, because it can be achieved both in vitro and in living organisms at the site of cell damage.

In the current study published in the journal Cell Stem Cell, Esteban Mazzoni and colleagues further investigated the process by which transcription factors bind to and activate parts of DNA during the first 48 hours after NIL expression. First, the researchers used single-cell RNA sequencing (RNA-seq) to study the timing of gene expression after induction by NIL programming factors. RNA-seq is a technique that reveals the presence and quantity of RNA in a sample at a specific point in time. Thus, as transcription factors turn genes on, these genes are transcribed into RNA that can be measured and quantified.

The researchers also studied chromatin remodeling during motor neuron programming. Chromatin is a tightly-packed form of DNA which regulates the expression of genes through changes in its structure. Promoters are regions of the DNA where transcription factors bind in order to initiate gene transcription. Chromatin must undergo structural changes, called remodeling, in order for the DNA to be accessible to transcription factors. Typically, as cells move through the differentiation process, chromatin changes that occur at promoter regions will restrict the differentiation potential of the cell.

To study this chromatin remodeling process, a ChIP-seq time series was performed. ChIP-seq combines chromatin immunoprecipitation with DNA sequencing to identify the binding sites of proteins that associate with DNA. Antibodies against the bound proteins are used to extract protein-DNA complexes, and the DNA binding sites can be sequenced. In addition, the researchers used an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) to study chromatin accessibility. Proteins called transposons incorporate into exposed, or accessible, portions of chromatin. Therefore, identifying the locations of transposons in the DNA can indicate what parts of the DNA are being actively transcribed, or turned on.

This series of experiments revealed information about how genes are turned on and off over the 48-hour process of motor neuron formation. Initially, the transcription factors Ngn2 and Isl1/Lhx3 induce different sets of genes in parallel. Whereas Ngn2 controls genes associated with generic neuronal differentiation, Isl1 and Lhx3 activate genes specific for spinal cord and motor neurons. As programming progresses, Ngn2 induces the expression of two other transcription factors, Ebf and Onecut. These transcription factors modify the chromatin state to enable Isl1/Lhx3 binding to previously inaccessible sites on the DNA that contain the terminal motor neuron genes necessary to complete the programming process.

These experiments showed that the activities of Ngn2 and Isl1/Lhx3 act in tandem to induce direct motor neuron programming from stem cells. The researchers hope to apply these findings clinically. By triggering this programming pathway in the body, cells in the spinal cord can be induced to differentiate into motor neurons, replacing the neurons that are damaged in diseases such as ALS.

References

Czarzasta J., Habich A., Siwek T., Czaplinski A., Maksymowicz W., Wojtikiewicz J. (2017) Stem cells for ALS: an overview of possible therapeutic approaches. Int J Dev Neurosci. DOI: 10.1016/j.ijdevneu.2017.01.003

Farrar M., Park S., Vucic S., Carey K., Turner B., Gillingwater T., Swoboda K., Kiernan M. (2016) Emerging therapies and challenges in Spinal Muscular Atrophy. Ann Neurol. DOI: 10.1002/ana.24864

Mazzoni, E.O., Mahony, S., Closser, M., Morrison, C.A., Nedelec, S., Williams, D.J., An, D., Gifford, D.K., and Wichterle, H. (2013). Synergistic binding of tran- scription factors to cell-specific enhancers programs motor neuron identity. Nat. Neurosci. 16:12191227. DOI:10.1038/nn.3467

Velasco S., Ibrahim M., Kakumanu A., Garipler G., Aydin B., Al-Sayegh M., Hirsekorn A., Abdul-Rahman F., Satija R., Ohler U., Mahony S., Mazzoni, E. (2016) A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells. Cell Stem Cell. DOI: 10.1016/j.stem.2016.11.006

Image via ColiN00B / Pixabay.

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New MRI Data from Asterias’ Ongoing SCiStar Clinical Study Indicates AST-OPC1 Cells Prevent Formation of … – PR Newswire (press release)

By Dr. Matthew Watson

"These new follow-up results based on MRI scans are very encouraging, and strongly suggest that AST-OPC1 cells have engrafted in these patients post-implantation and have the potential to prevent lesion cavity formation, possibly reducing long-term spinal cord tissue deterioration after spinal cord injury," said Dr. Edward Wirth, Chief Medical Officer of Asterias. "Moreover, these new results add to the overall body of data supporting AST-OPC1's safety, and are consistent with safety data from our previous Phase 1 study in thoracic spinal cord injury and our extensive preclinical studies in more than 3,000 animals."

Under the study protocol, patients are monitored by MRI scans at regular intervals over 12 months in order to assess status of the injection site and surrounding tissues.

The Company will discuss the MRI data in more detail on its first quarter 2017 conference call and webcast on May 11, 2017 at 4:30 p.m. Eastern / 1:30 p.m Pacific. For both "listen-only" participants and those participants who wish to take part in the question-and-answer session, the call can be accessed by dialing 800-533-7619 (U.S./Canada) or 785-830-1923 (international) five minutes prior to the start of the call and providing the Conference ID 7610291. To access the live webcast, go to http://asteriasbiotherapeutics.com/inv_events_presentations.php.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at http://www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. They also received low levels of immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with AST-OPC1. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all patients. In four of the five patients, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with cervical spine injuries, which represents the first targeted population for registration trials.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/new-mri-data-from-asterias-ongoing-scistar-clinical-study-indicates-ast-opc1-cells-prevent-formation-of-damaging-lesion-cavities-in-patients-suffering-severe-spinal-cord-injury-300455768.html

SOURCE Asterias Biotherapeutics, Inc.

http://www.asteriasbiotherapeutics.com

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New MRI Data from Asterias' Ongoing SCiStar Clinical Study Indicates AST-OPC1 Cells Prevent Formation of ... - PR Newswire (press release)

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Why Neuralstem Inc. (NASDAQ:CUR) can’t be predicted? – FinancialsTrend

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Science | UM researchers develop new technology for stem cell storage – Macau Daily Times

By raymumme

Home | Macau | Science | UM researchers develop new technology for stem cell storage

UM researchers have developed a new technology for cell storage and transport

The University of Macau (UM) Faculty of Health Sciences (FHS) has developed a technology that enables the storage of stem cells at room temperature for at least seven days without the loss of viability or biological activities. According to a statement issued by UM, this new technology does not rely on the traditional cryopreservation method which requires costly equipment and tedious cryopreservation procedures, thus enabling cell storage and transport under ambient conditions.

Under professor Ren-He Xus supervision, doctoral student Jiang Bin and postdoctoral researcher Yan Li, both from the FHS, engaged in the research study titled Spheroidal Formation Preserves Human Stem Cells for Prolonged Environment under Ambient Conditions for Facile Storage and Transportation. Together with the participation of Chris Wong Koon Ho, an assistant professor at the FHS, they successfully developed the new technology. The related paper has been published in Biomaterials, a renowned international journal in the field of biological materials.

The study found that preparing human mesenchymal stem cells (hMSC) to form spheroids with the hanging-drop or other methods, can reduce the cell metabolism and increase cell viability. Stored in a sealed vessel filled with regular culture medium, under ambient conditions without oxygen supply, the viability of hMSC in spheroids remained over 90 percent even after 11 days. This method is also applicable to higher pluripotent human embryonic stem cells.

Stem cells are found in various locations of the body such as bone marrow, blood, brain, spinal cord, skin, and corneal limbus. They are responsible for regenerating and repairing damaged tissues and organs in the body. Transplantation of stem cells can restore damaged tissues and organs to their original functions. For this reason, stem cells have significant clinical value. However, they require strict culturing and storage conditions. Extended exposure (over 24 to 48 hours) to unfavorable temperature, humidity, or levels of oxygen and carbon dioxide will cause the cells to gradually lose their functions and viability.

Currently, long-distance cell transport mainly relies on the costly method of cryopreservation. For short-distance transport, cells can be prepared in suspension or adherent culture, but the number of cells that can be transported via this method is limited. Moreover, cell viability decreases dramatically after transport for 48 hours under ambient conditions.

The UM claims that the new technology developed by its researchers can overcome the above limitations. With this technology, a sufficient dose of stem cells that are being transported can be used in patients without the need to freeze stem cells before transport and to thaw, revive, and proliferate the transported stem cells, a statement from the institution reads.

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Macao Researchers Develop Room Temperature Storage … – Live Trading News

By LizaAVILA

Macao Researchers Develop Room Temperature Storage Technology for Stem Cells

he University of Macao (UM) researchers developed a new way to store stem cells at room temperature for a minimum of 7 days without the loss of viability and biological activities, the universitys said in a press release Thursday.

UM said its researchers from Faculty of Health Sciences (FHS) has developed a technology which does not rely on the traditional cryopreservation method that requires costly equipment and tedious cryopreservation procedures, enabling cell storage and transport under ambient conditions.

Xu Renhe, a professor at the FHS of UM, has nearly two decades of research experiences in stem cells and their medical applications. He and his doctoral student Jiang Bin and postdoctoral researcher Yan Li, together with Dr. Chris Wong Koon Ho, an assistant professor at the FHS, engaged in the related research study titled Spheroidal Formation Preserves Human Stem Cells for Prolonged Environment under Ambient Conditions for Facile Storage and Transportation.

The related paper has been published in Biomaterials, a renowned international journal in the field of biological materials.

The study found that preparing human mesenchymal stem cells (hMSC) to form spheroids with the hanging-drop method or other methods can reduce the cell metabolism and increase the cell viability.

Stored in a sealed vessel filled with regular culture medium, under ambient conditions without oxygen supply, the viability of hMSC in spheroids remained over 90 percent even after 11 days. This method is also applicable to higher pluripotent human embryonic stem cells.

With this new technology, only regular culture tubes and media, which cost only several U.S. dollars, are required for storing and shipping probably any type of stem cells and non-stem cells that can aggregate, within a temperature range from 10 to 37C (centigrade).

Stem cells are found in various locations of the body such as bone marrow, blood, brain, spinal cord, skin, and corneal limbus. They are responsible for regenerating and repairing damaged tissues and organs in the body.

Have a terrific weekend.

cells, conditions, human, Macao, research, stem, storage, technology

Paul A. Ebeling, polymath, excels in diverse fields of knowledge. Pattern Recognition Analyst in Equities, Commodities and Foreign Exchange and author of The Red Roadmasters Technical Report on the US Major Market Indices, a highly regarded, weekly financial market letter, he is also a philosopher, issuing insights on a wide range of subjects to a following of over 250,000 cohorts. An international audience of opinion makers, business leaders, and global organizations recognizes Ebeling as an expert.

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Neural stem cell therapies could eventually play a role in treating spinal cord injuries – Medical Xpress

By NEVAGiles23

May 4, 2017 Neural stem cell therapies could eventually play a role in treating spinal cord injuries. Credit: woodoo007 / 123rf

Researchers in Qatar and Egypt, working with colleagues in Italy and the US, have found that injured spinal cords in rats show signs of tissue regeneration several weeks following injection with neural stem cells.

An estimated 2.5 million people worldwide live with spinal cord injury caused by various types of accidents and falls. "Much research is going into investigating the potential of stem cells in treating this and other neurological conditions," says Dr Hany Marei of Qatar University Biomedical Research Center.

The team isolated neural stem cells, which specifically differentiate into nerve tissue, from a structure in the front of the brain called the olfactory bulb. The olfactory bulbs were removed from human patients undergoing operations to extract brain tumours.

The team first genetically engineered the neural stem cells to carry a protein that causes them to fluoresce under the microscope. The researchers cultured the cells and demonstrated that they differentiated into a variety of nervous system cells.

They then injected the stem cells into rats whose spinal cords had been cut, and examined samples taken from the injured area regularly up until eight weeks after the injury. They compared these results with those of uninjured rats who did not receive injections, rats with injured cords that did not receive injections, and rats that underwent a sham operation in which the full procedure was done except for cutting of the spinal cord.

No signs of functional or tissue restoration were found in the control groups.

However, in the injured rats given neural stem cell injections, the team found that the stem cells differentiated into three types of nerve cells: oligodendrocytes and astrocyteswhich are involved in the production of the protective myelin sheath that surrounds nervesand neurons. There were no signs of immunorejection. However, there were also no signs of functional improvement in the rats in the form of movement of their hind limbs paralyzed by the injury.

The results indicate that injecting stem cells at sites of spinal cord injury can produce relatively normal neurons and other nervous tissue elements, but further studies are needed to promote locomotor recovery, says Marei. One possibility is that eight weeks (the upper limit in this study) is not enough time to restore damaged nerve tracts and neuronal circuitry.

Explore further: New hope for spinal cord injuries

Provided by: Qatar University

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CIRM California’s stem cell research funding agency to lose … – San Francisco Business Times

By NEVAGiles23

CIRM California's stem cell research funding agency to lose ...
San Francisco Business Times
Randy Mills, who came in to right California's semi-public stem cell research funding agency, is leaving to head the National Marrow Donor Program. Mills three ...
CA Stem Cell Agency Chief Randy Mills to Leave After Three Years ...Xconomy

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Stem cells were one of the biggest controversies of 2001. Where are they now? – Vox

By raymumme

Remember stem cells? They were one of the biggest scientific controversies during the early years of George W. Bushs presidency.

At the time, scientists had realized thatembryonic stem cells had the incredible capacity to transform into virtually any cell in the human body and so could potentially lead to new treatments or cures for a multitude of illnesses. On the other hand, extracting these stem cells required destroying human embryos, an action opposed by some pro-life individuals.

EMBRYONIC stem-cell THERAPIES ARE GETTING TESTED IN ACTUAL PATIENTS

The stem-cell debate got really heated. But then ... it just sort of fizzled out from public view. So whatever happened to stem cells?

A couple of things helped lessen the controversy. By the late 2000s, researchers discovered other ways to createcells similar to embryonic stem cells without destroying human embryos, a promising advance that helped defuse the culture-war aspect. Then, in 2009, Obama somewhat loosened the Bush-era restrictions on federal funding for stem-cell research and thecompromise seemed to quiet both sides down a fair amount.

So, lately, scientists have been patiently continuing their stem-cell research in a less noisy atmosphere. And that work has actually led to a few advances like restoring some sight in 10 patients with vision diseases. But the stem-cell controversy is far from dead. Researchers still might need cells from embryos to create certain treatments. If it turns out that non-embryonic stem cells aren't good enough, that could re-ignite the culture wars. So here's a guide to the debate:

Shinya Yamanaka (right) receiving flowers from Sweden's ambassador to Japan in 2012, after it was announced that Yamanaka won a Nobel Prize in medicine. (Jiji Press/AFP/Getty Images)

Embryonic stem cells attracted scientific attention because they have the potential to grow into virtually any cell in the human body say, insulin-producing cells for people with diabetes, brain cells for people with Parkinsons, or even wholenew organs to replace faulty ones.

But for many people, there was one huge ethical problem: creating them required destroying an embryo. That's why, in 2001,George W. Bush decided to limit federal funding of research to a list of 60 pre-existing embryonic stem-cell lines (so as to discourage the destruction of any more embryos). Many scientists viewed the rules as too strict. Hence the controversy.

Obama SOMEWHAT relaxed Bushs restrictions on embryonic stem cells

But then in 2007, Japanese scientistShinya Yamanaka and his colleagues managed to coax cells from adult humans into embryo-like flexibility. In other words, they were able to create cells that seemed to resemble embryonic stem cells but that didn't require destroying an embryo. (These new cells were named induced pluripotent stem cells, IPSCs.) Other researchers began finding that adult stem cells have similar, but more limited, properties, too.

Meanwhile, the politics shifted. In 2009, Barack Obama came into office and signed anexecutive order that somewhat relaxed Bushs restrictions on embryonic stem cells. Under the new rules, the federal government would fund work on new stem-cell lines, but only if they had been made from leftover embryos from fertility clinics andwith non-federal money. That compromise seemed tohelp thecontroversy settledown.

A figure of visual ability after an embryonic-stem-cell-derived treatment (red line) in patients with macular degeneration over the course of 360 days. (Schwartz et al., The Lancet, October 15, 2014)

While the controversy has calmed down, stem-cell research is taking off and scientists are making advances with both embryonic and non-embryonic cells.

Much of the initial research on stem-cell therapies has focused on eye treatments. (That's because stem-cell therapies can be unpredictable and have sometimes lead to tumors in previous experiments. A tumor in an eye would be relatively easier to deal with and remove than tumors hidden deeper inside the body.)

In October 2014, researchers from the company Advanced Cell Technology (now called Ocata Therapeutics)showed that they had created new retina cells from embryonic stem cells for 18 patients who were going blind. Afterward, 10 of them had improved eyesight. Another group of researchers in Japan is trying to do the same thing with non-embryonic cells (those aforementioned IPSCs).

10 PEOPLE WHO WERE GOING BLIND HAD Improved eyesight AFTER EMBRYONIC STEM-CELL THERAPY

Other embryonic stem-cell research has focused on developing cells that can help treat spinal-cord injuries. A company called Geron startedsafety tests in such patients in 2010.

Although a few groups are continuing to work on embryonic stem cells, many are now focusing on non-embryonic stem cells like IPSCs because they're less contentious. "Everyone jumped very, very quickly on the IPS[C] bandwagon because it was eligible for federal funding, and then also any of the controversy [regarding embryos] was dropped," says Susan Solomon, CEO of the nonprofit New York Stem Cell Foundation.

But Solomon also thinks researchers have moved away from embryonic stem cells too quickly. "We felt that it was way too early to do that," she adds. Her organization still studies embryonic stem cells, among others in part because they may be able to do things that non-embryonic stem cells can't. It's just too early to tell.

It's important to note that despite all the overhype over the years, stem-cell science has been moving at the same slow pace as most scientific fields. There are still no FDA-approved treatments that use either embryonic stem cells or IPSCs. And that means that controversy over whether embryonic stem cells are needed for science and medicine is still unresolved.

(Shutterstock)

That said, the fight over stem cells hasn't gone away forever. And there's likely to be more conflict in the future.

Even after the Obama administration relaxed the rules on funding stem-cell research, there are still plenty of hurdles. For example, federal funding is currently prohibited for research on embryonic stem-cell lines made through a technique calledSCNT or cloning, which requires creating embryos in the lab.

This technique could one day prove useful because it can turn a person's own cells into a customized embryonic stem-cell line and would therefore stop people's immune systems from rejecting stem-cell treatments.

In 2013 and 2014, two groups published the firstdemonstrations of this technique with human cells. But all such research in the US must be done with private funds.

On top of all of this, some states directly ban some or all stem-cell research within their borders no matter who's paying for it:

Note: Minnesota has a vague law on the books that's currently interpreted to mean that embryonic stem-cell research is ok. Missouri's law is a bit self-conflicting. For more details, check out The Hinxton Group's site, which includes quotations from the relevant regulations themselves.

"We went from more of a legislative vacuum to our current patchwork quilt, with legislation enacted in all of the jurisdictions where interest groups had enough clout to get the job done," Alan Regenberg, Director of Outreach and Research Support at the Johns Hopkins Berman Institute of Bioethics, told me in an email.

Several things could bring the stem-cell fight back. For example, a clinical trial could come out with some really impressive results on some sort of stem-cell treatment renewing the debate over whether regulations should be loosened. Conversely, a social conservative could run for president and bring up the ethical issues on the campaign trail. And no matter who lands in the White House in 2016, its reasonable to expect some major changes in federal policy and fast. Both George W. Bush and Barack Obama implemented their rules within the first year in office.

In 2013, Obama's stem-cell policy survived Supreme Court case Sherley v. Sebelius.

A piece on the first embryonic stem-cellmedical trials in people, by Sarah Boseley at the Guardian

Update: Clarified the current interpretation of Minnesota's stem cell laws and changed the map to match.

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New study reveals how embryonic cells make spinal cord, muscle … – Medical Xpress

By Dr. Matthew Watson

April 28, 2017 Neurons (red) and muscle cells (green) produced from NMPs in the laboratory. Credit: James Briscoe, Francis Crick Institute

A study from scientists at the Francis Crick Institute, the Max-Delbrck Center for Molecular Medicine, Berlin and the University of Edinburgh sheds new light on the cells that form spinal cord, muscle and bone tissue in mammalian embryos.

This discovery paves the way for generating these tissues from stem cells in the laboratory and could lead to new ways of studying degenerative conditions such as motor neuron disease and muscular dystrophy.

In embryos, the spinal cord, muscle and skeleton are produced from a group of cells called NMPs (neuro-mesodermal progenitors). These cells are few in number and exist only for a short time in embryos, despite giving rise to many tissues in the body. Their scarcity and inaccessibility has made studying NMPs challenging. Now, by using the latest molecular techniques, the research team has for the first time deciphered gene activity in NMPs. They used an advanced technique called single-cell transcriptional profiling, which analyses individual cells to provide a detailed picture of gene activity in every cell.

The technique allowed the team to establish a molecular signature of NMPs and to show that NMPs produced from stem cells in petri dishes in the laboratory closely resemble those found in embryos. This enabled the team to use lab-grown NMPs to learn more about these cells and how they make spinal cord, muscle and bone tissue. By manipulating the cells in petri dishes and testing the function of specific genes, the researchers re-constructed the regulatory mechanism and formulated a mathematical model that explains how NMPs produce the appropriate amounts of spinal cord and musculoskeletal cells.

Dr James Briscoe, who led the research from the Francis Crick Institute said:

"For embryonic development to progress smoothly, NMPs must make the right types of cells, in the right numbers at the right time. Understanding how cells such as NMPs make decisions is therefore central to understanding embryonic development. Single cell profiling techniques, including the ones we used in this study, are giving us unprecedented insight into this problem and offering a new and fascinating view of how embryos produce the different tissues that make up adults."

First author of the study Dr Mina Gouti, from the Max-Delbrck Center for Molecular Medicine, Berlin said:

"Improving our understanding of NMPs doesn't only answer an important developmental biology question but also holds great promise for regenerative medicine. It takes us a step closer to being able to use tissue from patients with diseases that affect muscles and motor neurons in order to study the causes and progress of these diseases. Being able to grow cells in the laboratory that faithfully resemble those found in the body is crucial for this."

The paper, A gene regulatory network balances neural and mesoderm specification during vertebrate trunk development, is published in Developmental Cell.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Mina Gouti et al. A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development, Developmental Cell (2017). DOI: 10.1016/j.devcel.2017.04.002

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esearchers from Hokkaido University in Japan together with an international team of scientists implanted specialized embryonic stem cells into the severed spinal cords of rats. The stem cells, called neural progenitor cells, ...

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New study reveals how embryonic cells make spinal cord, muscle ... - Medical Xpress

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Human head transplant: Dr Canavero considers Britain as the venue for 2017’s most talked about operation – Alphr

By Dr. Matthew Watson

A quick glance at your calendar will reveal that we're now in 2017. 2017, you may recall, is the year when contraversial surgeon Sergio Canavero has promised to perform the world's first human head transplant.

But just how feasible is a human head transplant? Is it the stuff of science fiction, or does it have a basis in current sceintific thinking? Read on for everything you need to know about 2017 most alarming scientific development.

A human head transplant is exactly what it sounds like taking one living head and putting it onto a new body.

But actually, thats a little misleading. In real terms, its a body transplant, as the head will be gaining a new body to control. However, as the term whole body transplant is already used to mean transferring the brain between bodies, calling it a head transplant makes it clear that the whole head is to be switched, brain included.

Until recently, a head transplant seemed totally implausible, but the Italian scientist Dr Sergio Canavero believes its possible, and intends to conduct the first surgery in 2017.

Canavero outlines the procedure in detail here, but these are the basics of the process. Remember: dont try this at home, kids.

The donor body and the head to be attached are first cooled down to 12-15C to ensure that the cells last longer than a few minutes without oxygen. The tissue around the neck is then cut, with the major blood vessels linked with tiny tubes. The spinal cord on each party is then severed cleanly with an extremely sharp blade.

"Post coma, Canavero believes the patient would immediately be able to move, feel their face and even speak with the same voice."

At this point, the head is ready to be moved, and the two ends of the spinal cord are fused using a chemical called polyethylene glycol, encouraging the cells to mesh. This chemical has been shown to prompt the growth of spinal cord nerves in animals, although Canavero suggests that introducing stem cells or olfactory ensheathing cells into the spinal cord could also be tried.

After the muscles and blood supply are successfully connected, the patient is kept in a coma for a month to limit movement of the newly fused neck, while electrodes stimulate the spinal cord to strengthen its new connections.

Following the coma, Canavero anticipates that the patient would immediately be able to move, feel their face and even speak with the same voice. He believes physiotherapy would allow the patient to walk within a year.

He explains his suggested methods in the TED talk below.

Sceptical would be a nice way of putting it. Horrified would, in most cases, be more accurate.

Dr Hunt Batjer has attracted headlines for being particularly blunt: I would not wish this on anyone. I would not allow anyone to do it to me as there are a lot of things worse than death.

Dr Jerry Silver witnessed the 1970s monkey head transplant experiment more on which later and describes the procedure as bad science, adding that just to do the experiments is unethical. This is a particular blow to Canavero, as he states that Silvers own work in reconnecting rats spinal cords should give hope to the human head transplant. Silver dismisses this: To sever a head and even contemplate the possibility of gluing axons back properly across the lesion to their neighbours is pure and utter fantasy in my opinion.

Dr Chad Gordon, professor of plastic and reconstructive surgery and neurological surgery at Johns Hopkins University, agrees that Canaveros claims are scientifically implausible. He told BuzzFeed: Theres no way hes going to hook up somebodys brain to someones spinal cord and have them be functional.

On the conservative side, were about 100 years away from being able to figure this out, he continued. If hes saying two, and hes promising a living, breathing, talking, moving human being? Hes lying.

Dr Paul Myers, associate professor of biology at the University of Minnesota at Morris, puts it even more explicitly: This procedure will not work... Try it with monkeys first. But he cant: the result would be, at best, a shambling horror, an animal driven mad with pain and terror, crippled and whimpering, and a poor advertisement for his experiment. And most likely what hed have is a collection of corpses that suffered briefly before expiring.

Others wonder whether Canavero might simply be enjoying the limelight with a PR stunt, including Dr Arthur Caplan, director of ethics at the NYU Langone Medical Centre. Describing the doctor as nuts, he explained to CNN: Their bodies would end up being overwhelmed with different pathways and chemistry than theyre used to, and theyd go crazy.

"We'll probably see a head on a robot before we see it on [another] body," he told Live Science.

Dr John Adler of Stanford University's school of medicine is slightly more optimistic... but not much more. "Conceptually, much of this could work, but the most favourable outcome will be little more than a Christopher Reeve level of function," he told Newsweek.

Canavero is aware of this criticism, claiming that silently hes received a lot of support from the medical community. Of Dr Batjers comments that the surgery would be a fate worse than death, Canavero is scathing. Hes a vascular surgeon. A vascular surgeon of the brain, yes, but he knows nothing, he argued. How can you say such a thing? Its incredible.

"The world is moving, the critics are dwindling. Of course, there will always be critics. Science teaches us that when you propose something groundbreaking, you must be confronted by criticism. If no critics really step forward, you are saying nothing special," he told Medical News Today.

Dr Canavero also believes that the operation could essentially be used to revive the dead, if brains were suitably frozen and stored. In an interview with German magazine Ooom, Canavero said: "We will try to bring the first of the company's patients back to life, not in 100 years. As soon as the first human head transplant has taken place, i.e. no later than 2018, we will be able to attempt to reawaken the first frozen head.We are currently planning the world's first brain transplant, and I consider it realistic that we will be ready in three years at the latest."

No-one has ever attempted a human head transplant before, and attempts on animals have to put it charitably had limited success.

Image: from Motherboard, uploaded under fair use from a 1959 issue of Life

The photo above really does show a dog with two heads and its not a fake. This was the work of Soviet scientist Vladimir Demikhov, and for four days the hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died.

Demikhov tried the experiment more than 24 times, but was unable to find a way of avoiding the dogs dying shortly after surgery. Although the results are horrifying to see, Demikhovs research did pave the way for human organ transplants.

"For four days this hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died."

But back to the topic of head transplants. The first time a straight swap was successful, was by Dr Robert White, in an experiment on a rhesus monkey in 1970. I feel the need to qualify the word successful with quotation marks, because although the monkey did live, he didnt live very long. Eight days, to be exact, and as the spinal cord wasnt attached to its new body, the monkey was paralysed for its remaining days. However, it could indeed see, hear, smell and taste before the body rejected the foreign head.

According to Canavero in his paper on human head transplants, the monkey lived eight days and was, by all measures, normal, having suffered no complications. However, Dr Jerry Silver who worked in the same lab as Dr White has more haunting memories. He toldCBS: I remember that the head would wake up, the facial expressions looked like terrible pain and confusion and anxiety in the animal. The head will stay alive, but not very long. It was just awful. I dont think it should ever be done again.

More recently, Chinese doctor Xiaoping Ren claims to have conducted head transplants on more than 1,000 mice. The Wall Street Journal reports to have witnessed a mouse with a new head moving, breathing, looking around and drinking. But, crucially, none of these mice have lived longer than a few minutes.

Still, Dr Rens studies continue, and the latest reports are said to be promising, offering a possible answer to the risk of severe blood loss (or brain ischemia) during transplantation. The experimental method that we have described can allow for long-term survival, and thus assessment of transplant rejection and central nervous system recovery, bringing us one step closer to AHBR in man, the researchers wrote.

Ren himself has not ruled out taking part in the first human head transplant operation, according to the Daily Mail. "A human head transplant will be a new frontier in science. Some people say it is the last frontier in medicine. It is a very sensitive and very controversial subject but if we can translate it to clinical practice, we can save a lot of lives," he said.

"Many people say a head transplant is not ethical. But what is the essence of a person? A person is the brain not the body. The body is just an organ," he added.

In January 2016, Canavero told New Scientist that a head transplant had been successfully completed on a monkey in China, although details were sparse. "The monkey fully survived the procedure without any neurological injury of whatever kind," he said, although the article notes that the monkey only kept alive for 20 hours after the surgery for "ethical reasons," limiting its use as a comparison somewhat.

In September 2016, Canavero revealeda further trial of the head transplant on dogs.New Scientisthas seen video footage of a dog appearing to walk three weeks after its spinal cord was severed, with Canavero claiming that the outcome is the result of the same techniques he plans to use on Spiridonov next year.

However, speaking to a number of scientists for their view on the new evidence, New Scientistcould find few sceptics converted. "These papers do not support moving forward in humans," said Jerry Silver a neuroscientist at Cape Western Reserve University in Ohio.

"The dog is a case report, and you cant learn very much from a single animal without controls. They claim they cut the cervical cord 90 per cent but theres no evidence of that in the paper, just some crude pictures," added Silver.

You could say so, though Canavero doesn't see it quite like that. In fact, controversially he sees it more as a failure of other types of medicine, telling Medical News Today, "It will be about curing incurable neurological disorders for which other treatments have failed big time, so gene therapy,stem cells- they all just came to nothing. We have failed despite billions of dollars being poured into this sort of research."

"So actually, head transplant or body transplant, whatever your angle is, is actually a failure of medicine. It is not a brilliant success, a brilliant advancement to medical science. When you just haven't tackled biology, you don't know how to treat genes, you don't really understand, and you really need to resort to a body transplant, it means that you've failed. So this must not be construed as a success of medical research," he added.

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Human head transplant: Dr Canavero considers Britain as the venue for 2017's most talked about operation - Alphr

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