Hip replacements, severe burns, spinal cord injuries, blast injuries, traumatic brain injuriesthese seemingly disparate traumas can each lead to a painful complication during the healing process called heterotopic ossification. Heterotopic ossification is abnormal bone formation within muscle and soft tissues, an unfortunately common phenomenon that typically occurs weeks after an injury or surgery. Patients with heterotopic ossification experience decreased range of motion, swelling and pain.

Currently, theres no way to prevent it and once its formed, theres no way to reverse it, says Benjamin Levi, M.D., Director of the Burn/Wound/Regeneration Medicine Laboratory and Center for Basic and Translational Research in Michigan Medicines Department of Surgery. And while experts suspected that heterotopic ossification was somehow linked to inflammation, new U-M research explains how this happens on a cellular scaleand suggests a way it can be stopped.

To help explain how the healing process goes awry in heterotopic ossification, the research team, led by Levi, Michael Sorkin, M.D. and Amanda Huber, Ph.D., of the Department of Surgerys section of plastic surgery, took a closer look at the inflammation process in mice. Using tissue from injury sites in mouse models of heterotopic ossification, they used single cell RNA sequencing to characterize the types of cells present. They confirmed that macrophages were among the first responders and might be behind aberrant healing.

Macrophages are white blood cells whose normal job is to find and destroy pathogens. Upon closer examination, the Michigan team found that macrophages are more complex than previously thoughtand dont always do what they are supposed to do.

Macrophages are a heterogenous population, some that are helpful with healing and some that are not, explains Levi. People think of macrophages as binary (M1 vs. M2). Yet weve shown that there are many different macrophage phenotypes or states that are present during abnormal wound healing.

Specifically, during heterotopic ossification formation, the increased presence of macrophages that express TGF-beta leads to an errant signal being sent to bone forming stem cells.

For now, the only way to treat heterotopic ossification is to wait for it to stop growing and cut it out which never completely restores joint function. This new research suggests that there may be a way to treat it at the cellular level. Working with the lab led by Stephen Kunkel, Ph.D. of the Department of Pathology, the team demonstrated that an activating peptide to CD47, p7N3 could alter TGF-beta expressing macrophages, reducing their ability to send signals to bone-forming stem cells that lead to heterotopic ossification.

During abnormal wound healing, we think there is some signal that continues to be present at an injury site even after the injury should have resolved, says Levi. Beyond heterotopic ossification, Levi says the studys findings can likely be translated to other types of abnormal wound healing like muscle fibrosis.

The team hopes to eventually develop translational therapies that target this pathway and further characterize not just the inflammatory cells but the stem cells responsible for the abnormal bone formation.

The paper is published in the journal Nature Communications. Other U-M authors include: Charles Hwang, William Carson IV, Rajarsee Menon, John Li, Kaetlin Vasquez, Chase Pagani, Nicole Patel, Shuli Li, Noelle D. Visser, Yashar Niknafs, Shawn Loder, Melissa Scola, Dylan Nycz, Katherine Gallagher, Laurie K. McCauley, Shailesh Agarwal, and Yuji Mishina.

Paper Cited: Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing, Nature Communications, DOI: 10.1038/s41467-019-14172-4

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Abnormal Bone Formation After Trauma Explained and Reversed in Mice - Michigan Medicine

Spinal Cord Stem Cells Comments Off on Abnormal Bone Formation After Trauma Explained and Reversed in Mice – Michigan Medicine | February 6th, 2020

It happens whenever there are news stories about a new treatment claiming to cure paralysis.

I get flooded with messages from distant relatives, or people I went to high school with but haven't seen in 10 years.

"OMG YOU TOTALLY NEED TO DO THIS."

I'm not saying other people shouldn't try whatever treatments they want to, but for me, there's too little certainty and too many unknown factors.

After 15 years in a wheelchair, I've gained the perspective that walking, in fact, does not equate happiness.

I'll never forget the metaphor used to explain to me how one would repair a spinal cord, even if I was a little high on morphine when I heard it.

I was 16, laying in a hospital bed with four large screws drilled into my skull to stabilize my spine.

"Imagine squeezing all of the toothpaste out of a tube. Now try and get that toothpaste back into the tube without changing it's shape or structure. That's how fragile your spinal cord is."

Sounds impossible, right? Maybe. Or maybe the technology just hasn't been invented yet.

The thing no one tells you about having a spinal cord injury is that not walking is the easiest adjustment. You don't need to check your eyes. You read that right.

The human body and muscle memory are pretty adaptable. Using a wheelchair is the easy part.

First, there are societal stigmas. They could fill their own novel.

Every person with a disability has a few horror stories. Personally, I applied to more than 600 jobs before getting a part-time, entry-level position. Shout out to the YMCA of Saskatoon for giving me a shot when no one else would!

Another thing that doesn't often get talked about is the secondary health issues that come along with a spinal cord injury. Low blood pressure, autonomic dysreflexia, inability to regulate your body temperature, bowel and bladder problems, and pressure sores to name a few.

These are the really hard parts.

These secondary health issues are why I have no interest in an epidural stimulation implant or any other elective surgery of that nature. I know it's exciting to see someone moving their leg after an injury or walking while assisted, but the truth is we don't know what other unknown factors such treatments might present.

I've seen plenty of stories about possible "cures." When I was first injured it was stem cells, then embryonic stem cells, then there were the paralyzed rats learning to walk again.

Every few years there's a new procedure that makes a splash. Everyone is positive that this time, this procedure, this one is the cure. None have come to fruition.

Hope and optimism are vital, but there's a fine line between hope and false hope. I've seen far too many people unable to overcome the false hope and remain bitter and angry that they can't be "normal."

The thing is, moving my leg or even walking (although it would be cool) wouldn't change the functional quality of my life. I'm already independent. I'm already quite happy with my life. Gaining the ability to move a leg still wouldn't address those secondary health issues.

I'm not saying any of these potential treatments aren't amazing advancements in medicine, but if you can't guarantee me the ability to sweat so I don't overheat in our prairie summers, or control of my bowels or bladder, it's not worth the unknowns or cost at this point in my life.

There's no guarantee. I won't compromise for a maybe.

This column is part of CBC'sOpinionsection. For more information about this section, please read thiseditor's blogand ourFAQ.

Interested in writing for us? We accept pitches for opinion and point-of-view pieces from Saskatchewan residents who want to share their thoughts on the news of the day, issues affecting their community or who have a compelling personal story to share. No need to be a professional writer!

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Yes, I've seen the stories about that new spinal treatment. Here's why I'm not interested - CBC.ca

Spinal Cord Stem Cells Comments Off on Yes, I’ve seen the stories about that new spinal treatment. Here’s why I’m not interested – CBC.ca | February 5th, 2020

Spinal cord injuries can result in severe neurological dysfunction, including motor, sensory, and autonomic paralysis, and up until now there has been no cure or effective treatment for such injuries.

But the first human trial based on Nobel Prize winning induced pluripotent stem cells (IPSC) technology, is due to start in Japan, giving hope to hundreds of thousands of paralysed patients, that there might be light at the end of their tunnel.

The spinal cord is responsible for relaying signals up and down the body from the brain to the nervous system. The spinal cord is a bundle of nerves contained in the spinal canal, which is cocooned in the spinal column (not to be confused with the spinal cord they are two very separate entities).

The spinal cord itself has a protective sheath wrapped around it which acts as insulation whilst allowing nerve signals from the brain to travel even faster to where they need to go.

The spinal column is divided into five distinct sections:

The site of the spinal cord injury will determine the severity of the injury and injuries are classified as either:

The higher up the spinal cord the injury occurs, the more function and feeling will be lost. It is estimated that approximately every year there are between 8 to 246 cases per million incidences of spinal cord injuries worldwide.

Stem cell therapy is amongst the most exciting ongoing research for people with spinal cord injuries, in modern medicine. Because whilst the research is still in its infancy, legitimate trials are showing promising results.

According to the Journal of the American Academy of Orthopedic Surgeons, there are different stem cells which have varying abilities to restore certain functions.

Stem cells are self-renewing cells that can differentiate into one or more specific cell types. For people with spinal cord injuries, stem cells could prevent further cell death, stimulate cell growth from the existing cells and even replace the injured cells, restoring the communication channels between the body and the brain.

Until recently, stem cell research has involved looking at:

It is research into these induced pluripotent stem cells that the team in Japan are currently laying down the groundwork for. They are planning to conduct a first-in-human study of an induced pluripotent stem cell-based intervention, for subacute spinal cord injury.

Not only that, but it is the first such therapy to look into treating this kind of injury, that has ever received government approval for sale to patients.

However there are concerns by those who work in the field, but arent working on this particular project, that the evidence to support the suggestion that the treatment works, is insufficient. They state that the approval for the research was based on a small, poorly designed clinical trial.

Like the majority of scientific breakthroughs that have gone before, there will always be naysayers we used to think the world was flat and the sun orbited Earth, that the body was composed of four humours and an imbalance in those made us sick.

Those theories were disproved, and look how far weve come since then. Now imagine if we could make a paralysed person walk again. It will happen. But for now, lets celebrate and support this team for trying.

Because whilst there have been multiple attempts to develop stem cell transplantation approaches with the aim to regenerate damaged spinal cords before, this multicentre team is planning the first that might actually work, and be ethical to boot.

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Stem Cell Regeneration for Spinal Cord injuries

Spinal Cord Stem Cells Comments Off on Stem Cell Regeneration for Spinal Cord injuries | February 4th, 2020

SAN ANTONIO, Feb. 3, 2020 /PRNewswire/ -- SASpine is now offering cutting edge Stem Cell Treatments to patients. For the past several years Dr. Steven Cyr, Mayo Clinic Trained Spine Surgeon, has been researching the benefits of stem cells in the treatment of multiple medical conditions including spinal disorders, specifically, conditions which involve spinal cord injury, degenerative disc disease, herniated discs, and as a supplement to enhance the success of Spinal fusions when treating instability, deformity, and fractures of the spine.

Steven J. Cyr, M.D., is a spine surgeon who has gained a reputation for surgical excellence in Texas, throughout the nation, and abroad.

Dr. Steven Cyr has been treating patients using growth factors and stem cells contained in amniotic tissue and bone marrow aspirate to provide a potential for improved success with fusion procedures, when treating herniated discs, and for arthritic or damaged joints, with remarkable success. "The goal of any medical intervention is to yield improved outcomes with the ideal result of returning a patient to normal function, when possible," states Dr Cyr. He went on to elaborate that there are times when only a structural solution can solve problems related to spinal disorders, but even in that scenario, the use of stem cells or growth factors derived from stem cell products can possibly improve the success of surgical procedures. "I have patients previously unable to jog or run return to normal function and athletic ability after injections of growth factors and stem cell products into the knee joints, hip joints, and shoulder joints," he said. "This includes high-level athletes, professional dancers, and the average weekend warrior."

There may be promise in treating patients with spinal cord injury as well. SASpine CEO, LeAnn Cyr, states, "There are reports of patients gaining significant neurological improvement after being treated with stem cells." Dr Cyr continues, "Most patients with spinal cord injuries resulting from trauma also have mechanical pressure on the nerves that result either from bone fragments or disc material compressing the spinal cord that needs to be removed along with surgical stabilization of the spinal bones. There's significant potential that stem cells bring to the equation when treating these types of patients, and I am excited about the potential that these products offer to the host of treatments to address spinal conditions and arthritic joints."

For more information about SASpine's Stem Cell Treatment Program, visit http://www.saspine.com or call (210) 487-7463 in San Antonio or (832) 919-7990 in Houston.

Related Linkswww.facebook.com/saspinewww.instagram.com/surgical.associates.in.spine

If you've been living with back pain, you're not alone. Here at SASpine, we have experienced spine specialists who are committed to improving your quality of life. (PRNewsfoto/SASpine)

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SASpine to offer Stem Cell Therapy - Yahoo Finance

Spinal Cord Stem Cells Comments Off on SASpine to offer Stem Cell Therapy – Yahoo Finance | February 3rd, 2020

A patient who received the worlds first transplant of cardiac muscle cells using artificially derived stem cells known as iPS cells this month is in stable condition, an Osaka University team said Jan. 27.

After surgery, doctors closely monitored the patient, who had ischemic cardiomyopathy, a condition in which clotted arteries cause heart muscles to malfunction. But the patient has been moved toa general hospital ward, the team said.

Yoshiki Sawa, a professor of cardiovascular surgery at the university, who led the team that conducted the transplant, said the team aims to put the technique into practical use.

Sawa said the team hopestransplants of heart muscle tissues derived from induced pluripotent stem cellswill be used to save many patients who have heart conditions.

In the clinical trial, three sheets of heart muscle tissues made from iPS cells stocked at Kyoto Universitys Center for iPS Cell Research and Application were attached to affected parts of the patients heart. The iPS cells were created from tissues provided by a healthy donor.

The sheets were 4 to 5 centimeters in diameter and 0.1 millimeter thick.

The transplant's goal is to regenerate cardiac blood vessels using a substance secreted by the sheets of muscle cells. The sheets are degradable and disappear from the body several months after they secrete the substance, according to the team.

The university plans to perform similar transplants on nine other patients who have serious heart problems.

The Osaka University team had planned to conduct the clinical trial of the transplant earlier after the government approved the plan in May 2018.

But it was postponed due to damage from a powerful earthquake that hit Osaka Prefecture the following month that rendered its facility to cultivate cells unusable.

The trial is part of the process toward the future distribution of medical products using cells.

Osaka Universitys announcement of the successful transplant of tissues created from iPS cells marked the fourth such transplantation.

Including Osaka University's trial, Japanese surgeons have now successfully transplanted tissues created from iPS cells four times.

The world's first transplant of iPS-derived cells was conducted in 2014 whenthe Riken research institute transplanted retina cells for a patient with age-related macular degeneration.

In 2018, Kyoto University transplanted nerve cells for a Parkinson disease patient. Osaka University transplanted cornea cells into a patient with a disease of the cornea in 2019.

Patients who undergo transplants using iPS-derived cell must accept the risk that the cells may become cancerous.

The moreiPS-derived cells a patient receives, the higher their risk.

Hundreds of thousands of retina cells were used in the 2014 retina transplant. In the 2018 and 2019 transplants, the number of nerve and cornea cells used soared to between 5 million to 6 million.

Osaka University's latest transplant utilized roughly 100 milliontissues made from iPS cells.

Sawa acknowledged the transplanted heart muscle tissues could turn cancerous, but said the teamhas made great efforts to remove potentially cancerous cells.

Hideyuki Okano, professor of molecular neurobiology at Keio University, who is researching the application of iPS-derived nerve cells to treat patients with spinal cord damage, said the risk was worth it.

Okano said the Osaka University's transplant, using tissues made from iPS cells from a donor, could be more effective than the existing therapy, which uses the patients own muscle tissues.

I understand that the transplanted tissues might become cancerous or cause an erratic heart rhythm, but the transplantation of the iPS-derived heart muscle tissues can be more effective than muscle tissue sheets made from the patients leg, Okano said.

Keio University is also planning to conduct clinical research using iPS-derived cells to regenerate heart tissues.

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Patient in Japan 1st to have iPS cell heart muscle transplant : The Asahi Shimbun - Asahi Shimbun

Spinal Cord Stem Cells Comments Off on Patient in Japan 1st to have iPS cell heart muscle transplant : The Asahi Shimbun – Asahi Shimbun | February 3rd, 2020

Neuralstem (NASDAQ:CUR) and SpringWorks Therapeutics (NASDAQ:SWTX) are both small-cap medical companies, but which is the better investment? We will contrast the two companies based on the strength of their analyst recommendations, earnings, institutional ownership, profitability, valuation, dividends and risk.

Earnings & Valuation

This table compares Neuralstem and SpringWorks Therapeutics gross revenue, earnings per share and valuation.

SpringWorks Therapeutics has lower revenue, but higher earnings than Neuralstem.

Institutional and Insider Ownership

38.3% of Neuralstem shares are owned by institutional investors. Comparatively, 72.1% of SpringWorks Therapeutics shares are owned by institutional investors. 5.4% of Neuralstem shares are owned by insiders. Strong institutional ownership is an indication that hedge funds, endowments and large money managers believe a stock is poised for long-term growth.

Profitability

This table compares Neuralstem and SpringWorks Therapeutics net margins, return on equity and return on assets.

Analyst Ratings

This is a summary of current ratings and target prices for Neuralstem and SpringWorks Therapeutics, as reported by MarketBeat.

SpringWorks Therapeutics has a consensus price target of $35.50, suggesting a potential upside of 12.77%. Given SpringWorks Therapeutics higher possible upside, analysts plainly believe SpringWorks Therapeutics is more favorable than Neuralstem.

Summary

SpringWorks Therapeutics beats Neuralstem on 6 of the 8 factors compared between the two stocks.

Neuralstem Company Profile

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The company's stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. Its lead product candidate is NSI-189, a chemical entity, which has been completed Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical study for the treatment-refractory depression, Angelman Syndrome, Alzheimer's disease, ischemic stroke, diabetic neuropathy, irradiation-induced cognitive deficit, and long-term potentiation enhancement. The company also develops NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease; Phase II clinical trial for the treatment of chronic ischemic stroke; and Phase I clinical trials for the treatment of chronic spinal cord injury, as well as is in preclinical study for the traumatic brain injury. In addition, it develops NSI-532, which is in preclinical study for treatment of Alzheimer's disease; and NSI-777 that is in preclinical study for treatment of human demyelinating diseases. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

SpringWorks Therapeutics Company Profile

SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company, acquires, develops, and commercializes medicines for underserved patient populations suffering from rare diseases and cancer. Its advanced product candidate is nirogacestat, an oral small molecule gamma secretase inhibitor that is in Phase 3 clinical trials for the treatment of desmoid tumors. The company is also developing mirdametinib, an oral small molecule MEK inhibitor that is in Phase 2b clinical trials for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas; and Nirogacestat + belantamab mafodotin, which is in Phase 1b clinical trials for the treatment of relapsed or refractory multiple myeloma. In addition, it is developing Mirdametinib + lifirafenib, a combination therapy that is in Phase 1b clinical trials in patients with advanced or refractory solid tumors; and BGB-3245, an investigational oral selective small molecule inhibitor of specific BRAF driver mutations and genetic fusions, which is in preclinical studies in a range of tumor models with BRAF mutations or fusions. The company has collaborations with BeiGene, Ltd. and GlaxoSmithKline plc to develop combination approaches with nirogacestat and mirdametinib, as well as other standalone medicines. SpringWorks Therapeutics, Inc. was founded in 2017 and is headquartered in Stamford, Connecticut.

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Neuralstem (NASDAQ:CUR) & SpringWorks Therapeutics (NASDAQ:SWTX) Financial Review - Riverton Roll

Spinal Cord Stem Cells Comments Off on Neuralstem (NASDAQ:CUR) & SpringWorks Therapeutics (NASDAQ:SWTX) Financial Review – Riverton Roll | February 2nd, 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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First pain treatment using human stem cells developed - THE WEEK

Spinal Cord Stem Cells Comments Off on First pain treatment using human stem cells developed – THE WEEK | January 31st, 2020

As they do in many areas of medicine, stem cells hold great potential in treating injured spinal cords, but getting them where they need to go is a delicate undertaking. Scientists at the University of California San Diego (UCSD) are now reporting a breakthrough in this area, demonstrating a new injection technique in mice they say can deliver far larger doses of stem cells and avoid some of the dangers of current approaches.

The research focuses on the use of a type of stem cell known as a neural precursor cell, which can differentiate into different types of neural cells and hold great potential in repairing damaged spines. Currently, these are directly injected into the primary cord of nerve fibers called the spinal parenchyma.

As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding, says Martin Marsala, professor in the Department of Anesthesiology at UCSD School of Medicine.

In experiments on rodents, Marsala and his team have demonstrated a safer and less invasive approach. The scientists instead injected the stem cells in between a protective layer around the spine called the pial membrane and the superficial layers of the spinal cord, a region known as the spinal subpial space.

This injection technique allows the delivery of high cell numbers from a single injection, says Marsala. Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells.

Following these promising early results, the scientists are hopeful that stem cells injected in this way could one day greatly accelerate healing and improve the strength of cell-replacement therapies for several spinal neurodegenerative disorders, including spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis. But first will come experiments on larger animal models closer to the human anatomy in size, which will help them fine tune their technique for the best results.

The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect, says Marsala.

The research was published in the journal Stem Cells Translational Medicine.

Source: University of California San Diego

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Spinal injury researchers find a sweet spot for stem cell injections - New Atlas

Spinal Cord Stem Cells Comments Off on Spinal injury researchers find a sweet spot for stem cell injections – New Atlas | January 31st, 2020

As amphibians go, axolotls are pretty cute. These salamanders sport a Mona Lisa half-smile and red, frilly gills that make them look dressed up for a party. You might not want them at your soiree, though: Theyre also cannibals. While rare now in the wild, axolotls used to hatch en masse, and it was a salamander-eat-salamander world. In such a harsh nursery, they evolved or maybe kept the ability to regrow severed limbs.

Their regenerative powers are just incredible, says Joshua Currie, a biologist at the Lunenfeld-Tanenbaum Research Institute in Toronto whos been studying salamander regeneration since 2011. If an axolotl loses a limb, the appendage will grow back, at just the right size and orientation. Within weeks, the seam between old and new disappears completely.

And its not just legs: Axolotls can regenerate ovary and lung tissue, even parts of the brain and spinal cord.

The salamanders exceptional comeback from injury has been known for more than a century, and scientists have unraveled some of its secrets. It seals the amputation site with a special type of skin called wound epithelium, then builds a bit of tissue called the blastema, from which sprouts the new body part. But until recently, the fine details of the cells and molecules needed to create a leg from scratch have remained elusive.

With the recentsequencingandassemblyof the axolotls giant genome, though, and thedevelopment of techniques to modify the creatures genes in the lab,regeneration researchers are now poised to discover those details. In so doing, theyll likely identify salamander tricks that could be useful in human medicine

Already, studies are illuminating the cells involved, and defining the chemical ingredients needed. Perhaps, several decades from now, people, too, might regrow organs or limbs. In the nearer future, the findings suggest possible treatments for ways to promote wound-healing and treat blindness.

The idea of human regeneration has evolved from an if to a when in recent decades, says David Gardiner, a developmental biologist at the University of California, Irvine. Everybody now is assuming that its just a matter of time, he says. But, of course, theres still much to do.

In a working limb, cells and tissues are like the instruments in an orchestra: Each contributes actions, like musical notes, to create a symphony. Amputation results in cacophony, but salamanders can rap the conductors baton and reset the remaining tissue back to order and all the way back to the symphonys first movement, when they first grew a limb in the embryo.

The basic steps are known: When a limb is removed, be it by hungry sibling or curious experimenter, within minutes the axolotls blood will clot. Within hours, skin cells divide and crawl to cover the wound with a wound epidermis.

Next, cells from nearby tissues migrate to the amputation site, forming a blob of living matter. This blob, the blastema, is where all the magic happens, said Jessica Whited, a regenerative biologist at Harvard University, in a presentation in California last year. It forms a structure much like the developing embryos limb bud, from which limbs grow.

This movie shows immune cells, labeled to glow green, moving within a regenerating axolotl fingertip. Scientists know that immune cells such as macrophages are essential for regeneration: When they are removed, the process is blocked.

Finally, cells in the blastema turn into all the tissues needed for the new limb and settle down in the right pattern, forming a tiny but perfect limb. This limb then grows to full size. When all is done, you cant even tell where the amputation occurred in the first place, Whited tellsKnowable Magazine.

Scientists know many of the molecular instruments, and some of the notes, involved in this regeneration symphony. But its taken a great deal of work.

As Currie started as a new postdoc with Elly Tanaka, a developmental biologist at the Research Institute of Molecular Pathology in Vienna, he recalls wondering, Where do the cells for regeneration come from? Consider cartilage. Does it arise from the same cells as it does in the developing embryo, called chondrocytes, that are left over in the limb stump? Or does it come from some other source?

To learn more, Currie figured out a way to watch individual cells under the microscope right as regeneration took place. First, he used a genetic trick to randomly tag the cells he was studying in a salamander with a rainbow of colors. Then, to keep things simple, he sliced off just a fingertip from his subjects. Next, he searched for cells that stuck out say, an orange cell that ended up surrounded by a sea of other cells colored green, yellow and so on. He tracked those standout cells, along with their color-matched descendants, over the weeks of limb regeneration. His observations, reported in the journalDevelopmental Cellin 2016,illuminated several secrets to the regeneration process.

Regenerative biologist Joshua Currie labeled the cells in axolotls with a rainbow of colors, so that he could follow their migration after he amputated the tip of the salamanders fingertips. In this image, three days after amputation, the skin (uncolored) has already covered the wound. (Credit: Josh Currie)

For one thing, cell travel is key. Cells are really extricating themselves from where they are and crawling to the amputation plane to form this blastema, Currie says. The distance cells will journey depends on the size of the injury. To make a new fingertip, the salamanders drew on cells within about 0.2 millimeters of the injury. But in other experiments where the salamanders had to replace a wrist and hand, cells came from as far as half a millimeter away.

More strikingly, Currie discovered that contributions to the blastema were not what hed initially expected, and varied from tissue to tissue. There were a lot of surprises, he says.

Chondrocytes, so important for making cartilage in embryos, didnt migrate to the blastema (earlier in 2016, Gardiner and colleaguesreported similar findings). And certain cells entering the blastema pericytes, cells that encircle blood vessels were able to make more of themselves, but nothing else.

The real virtuosos in regeneration were cells in skin called fibroblasts and periskeletal cells, which normally surround bone. They seemed to rewind their development so they could form all kinds of tissues in the new fingertip, morphing into new chondrocytes and other cell types, too.

To Curries surprise, these source cells didnt arrive all at once. Those first on the scene became chondrocytes. Latecomers turned into the soft connective tissues that surround the skeleton.

How do the cells do it? Currie, Tanaka and collaborators looked at connective tissues further, examining the genes turned on and off by individual cells in a regenerating limb. In a 2018Sciencepaper, the team reported thatcells reorganized their gene activation profileto one almost identical, Tanaka says, to those in the limb bud of a developing embryo.

Muscle, meanwhile, has its own variation on the regeneration theme. Mature muscle, in both salamanders and people, contains stem cells called satellite cells. These create new cells as muscles grow or require repair. In a 2017 study inPNAS, Tanaka and colleagues showed (by tracking satellite cells that were made to glow red) that most, if not all, ofmuscle in new limbs comes from satellite cells.

If Currie and Tanaka are investigating the instruments of the regeneration symphony, Catherine McCusker is decoding the melody they play, in the form of chemicals that push the process along. A regenerative biologist at the University of Massachusetts Boston, she recently published arecipe of sorts for creating an axolotl limb from a wound site. By replacing two of three key requirements with a chemical cocktail, McCusker and her colleagues could force salamanders to grow a new arm from a small wound on the side of a limb, giving them an extra arm.

Using what they know about regeneration, researchers at the University of Massachusetts tricked upper-arm tissue into growing an extra arm (green) atop the natural one (red). (Credit: Kaylee Wells/McCusker Lab)

The first requirement for limb regeneration is the presence of a wound, and formation of wound epithelium. But a second, scientists knew, was a nerve that can grow into the injured area. Either the nerve itself, or cells that it talks to, manufacture chemicals needed to make connective tissue become immature again and form a blastema. In their 2019 study inDevelopmental Biology, McCusker and colleagues guided byearlier work by a Japanese team used two growth factors, called BMP and FGF, to fulfill that step in salamanders lacking a nerve in the right place.

The third requirement was for fibroblasts from opposite sides of a wound to find and touch each other. In a hand amputation, for example, cells from the left and right sides of the wrist might meet to correctly pattern and orient the new hand. McCusckers chemical replacement for this requirement was retinoic acid, which the body makes from vitamin A. The chemical plays a role in setting up patterning in embryos and has long been known to pattern tissues during regeneration.

In their experiment, McCuskers team removed a small square of skin from the upper arm of 38 salamanders. Two days later, once the skin had healed over, the researchers made a tiny slit in the skin and slipped in a gelatin bead soaked in FGF and BMP. Thanks to that cocktail, in 25 animals the tissue created a blastema no nerve necessary.

About a week later, the group injected the animals with retinoic acid. In concert with other signals coming from the surrounding tissue, it acted as a pattern generator, and seven of the axolotls sprouted new arms out of the wound site.

The recipe is far from perfected: Some salamanders grew one new arm, some grew two, and some grew three, all out of the same wound spot. McCusker suspects that the gelatin bead got in the way of cells that control the limbs pattern. The key actions produced by the initial injury and wound epithelium also remain mysterious.

Its interesting that you can overcome some of these blocks with relatively few growth factors, comments Randal Voss, a biologist at the University of Kentucky in Lexington. We still dont completely know what happens in the very first moments.

If we did know those early steps, humans might be able to create the regeneration symphony. People already possess many of the cellular instruments, capable of playing the notes. We use essentially the same genes, in different ways, says Ken Poss, a regeneration biologist at the Duke University Medical Center in Durham who describednew advances in regeneration, thanks to genetic tools, in the 2017Annual Review of Genetics.

Regeneration may have been an ability we lost, rather than something salamanders gained. Way back in our evolutionary past, the common ancestors of people and salamanders could have been regenerators, since at least one distant relative of modern-day salamanders could do it. Paleontologists have discovered fossils of300-million-year-old amphibians with limb deformities typically created by imperfect regeneration.Other members of the animal kingdom, such as certain worms, fish and starfish, can also regenerate but its not clear if they use the same symphony score, Whited says.

These fossils suggest that amphibians calledMicromelerpetonwere regenerating limbs 300 million years ago. Thats because the fossils show deformities, such as fused bones, that usually occur when regrowth doesnt work quite right. (Credit: Nadia B Frbisch et al./Proceedings of the Royal Society B, 2014)

Somewhere in their genomes, all animals have the ability, says James Monaghan, a regeneration biologist at Northeastern University in Boston. After all, he points out, all animals grow body parts as embryos. And in fact, people arent entirely inept at regeneration. We can regrow fingertips, muscle, liver tissue and, to a certain extent, skin.

But for larger structures like limbs, our regeneration music falls apart. Human bodies take days to form skin over an injury, and without the crucial wound epithelium, our hopes for regeneration are dashed before it even starts. Instead, we scab and scar.

Its pretty far off in the future that we would be able to grow an entire limb, says McCusker. I hope Im wrong, but thats my feeling.

She thinks that other medical applications could come much sooner, though such as ways to help burn victims. When surgeons perform skin grafts, they frequently transfer the top layers of skin, or use lab-grown skin tissue. But its often an imperfect replacement for what was lost.

Thats because skin varies across the body; just compare the skin on your palm to that on your calf or armpit. The tissues that help skin to match its body position, giving it features like sweat glands and hair as appropriate, lie deeper than many grafts. The replacement skin, then, might not be just like the old skin. But if scientists could create skin with better positional information, they could make the transferred skin a better fit for its new location.

Monaghan, for his part, is thinking about regenerating retinas for people who have macular degeneration or eye trauma. Axolotls can regrow their retinas (though, surprisingly, their ability to regenerate the lens is limited to hatchlings). He is working with Northeastern University chemical engineer Rebecca Carrier, whos been developing materials for use in transplantations. Her collaborators are testing transplants in pigs and people, but find most of the transplanted cells are dying. Perhaps some additional material could create a pro-regeneration environment, and perhaps axolotls could suggest some ingredients.

Carrier and Monaghan experimented with the transplanted pig cells in lab dishes, and found they were more likely to survive and develop into retinal cells if grown together with axolotl retinas. The special ingredientseems to be a distinct set of chemicals that exist on axolotl, but not pig, retinas.Carrier hopes to use this information to create a chemical cocktail to help transplants succeed. Even partially restoring vision would be beneficial, Monaghan notes.

Thanks to genetic sequencing and modern molecular biology, researchers can continue to unlock the many remaining mysteries of regeneration: How does the wound epithelium create a regeneration-promoting environment? What determines which cells migrate into a blastema, and which stay put? How does the salamander manage to grow a new limb of exactly the right size, no larger, no smaller? These secrets and more remain hidden behind that Mona Lisa smile at least for now.

10.1146/knowable-012920-1

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

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What the Axolotl's Limb-Regenerating Capabilities Have to Teach Us - Discover Magazine

Spinal Cord Stem Cells Comments Off on What the Axolotl’s Limb-Regenerating Capabilities Have to Teach Us – Discover Magazine | January 31st, 2020

An international research team, led by physician-scientists at University of California San Diego School of Medicine, describe a new method for delivering neural precursor cells (NSCs) to spinal cord injuries in rats, reducing the risk of further injury and boosting the propagation of potentially reparative cells.NSCs hold great potential for treating a variety of neurodegenerative diseases and injuries to the spinal cord. The stem cells possess the ability to differentiate into multiple types of neural cell, depending upon their environment. As a result, there is great interest and much effort to use these cells to repair spinal cord injuries and effectively restore related functions.

But current spinal cell delivery techniques, said Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine, involve direct needle injection into the spinal parenchyma the primary cord of nerve fibers running through the vertebral column. "As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding," said Marsala.

The new technique is less invasive, depositing injected cells into the spinal subpial space a space between the pial membrane and the superficial layers of the spinal cord.

"This injection technique allows the delivery of high cell numbers from a single injection," said Marsala. "Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells."

Marsala, senior author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health, and colleagues suggest that subpially-injected cells are likely to accelerate and improve treatment potency in cell-replacement therapies for several spinal neurodegenerative disorders in which a broad repopulation by glial cells, such as oligodendrocytes or astrocytes, is desired.

"This may include spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis," said Ciacci.

The researchers plan to test the cell delivery system in larger preclinical animal models of spinal traumatic injury that more closely mimic human anatomy and size. "The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect," said Marsala.ReferenceMarsala et al. (2019) Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats. Stem Cells Translational Medicine. DOI: https://doi.org/10.1002/sctm.19-0156

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Injection Innovation May Improve Spinal Cord Repair Research - Technology Networks

Spinal Cord Stem Cells Comments Off on Injection Innovation May Improve Spinal Cord Repair Research – Technology Networks | January 30th, 2020

Spinal cord injury (SCI) is a common disease with high incidence, disability rate and treatment cost. microRNA (miR)-200a is reported to inhibit Keap1 to activate Nrf2 signaling. This study aimed to explore the effects of lentivirus-mediated miR-200a gene-modified bone marrow mesenchymal stem cells (BMSCs) transplantation on the repair of SCI in a rat model. BMSCs were isolated from the bone marrow of Sprague-Dawley rats. miR-200a targeting to Keap1 was identified by luciferase-reporter gene assay. The expressions of Keap1, Nrf2, NQO-1, HO-1 and GCLC were detected by Western blotting in SCI rats. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan scale. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured. miR-200a inhibited Keap-1 3 UTR activity in BMSCs. Transplantation of BMSCs with overexpression of miR-200a or si-Keap1increased locomotor function recovery of rats after SCI, while decreased MDA level, increased SOD, CAT activities and Nrf2 expression together with its downstream HO-1, NQO1, GCLC protein expressions in SCI rat. These results indicated that overexpressed miR-200a in BMSCs promoted SCI repair, which may be through regulating anti-oxidative signaling pathway. 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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Upregulation of microRNA-200a in bone marrow mesenchymal stem cells enhances the repair of spinal cord injury in rats by reducing oxidative stress and...

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In the 1986 horror classic The Fly, a scientist played by Jeff Goldblum manages, quite unintentionally, to mix his biology with that of a housefly with gruesome results.

But the real-world mutant fruit flies that scientists used to understand body patterning are almost as bizarre: Flies with legs on their brows instead of antennae. Flies with extra chest sections, complete with duplicate wings. Flies missing big chunks of their heads.

These freaky flies have something in common: Theyre mixing up their head-to-tail body plans. And they earned three scientists the Nobel Prize in Physiology or Medicine in 1995.

Two of the scientists, Eric Wieschaus and Christiane Nsslein-Volhard, conducted a now-famous genetic screen of fruit fly embryos in 1979 and 1980 while working at the European Molecular Biology Laboratory in Heidelberg, Germany. By feeding parent flies a powerful mutagen, they created a horde of larvae with genetic mistakes, including ones that affected how the fly embryo arranges bits of tissue, from head to tail, in sections a process called segmentation. (The pair tell the tale of this landmark experiment in the 2016 Annual Review of Cell and Developmental Biology.)

The other Nobel laureate, Edward Lewis of Caltech, discovered key players, later named Hox genes, that tell these fruit fly segments and other body parts what tissues and structures they should become.

Fruit flies, it turns out, have their own segmentation path, different from ours: They make a big chunk of tissue and then slice it up, like one would a loaf of bread. In contrast, vertebrates (including humans) churn out segments one by one, like a string of sausages, as they build the tissue. But many of the genes involved Hox and others found later are the same.

A landmark genetics screen by two scientists unearthed mutants with segmentation defects in the fruit fly Drosophila. On the left is the outer layer, or cuticle, of a normal early larva. To the right are ones of various mutants, with clear abnormalities.

CREDIT: E. WIESCHAUS & C. NSSLEIN-VOLHARD / AR CELL AND DEVELOPMENTAL BIOLOGY 2016

These commonalities extend to the need for a sort of ruler that guides segmentation and Hox actions by helping cells identify their position in the body. That ruler takes the form of a two-way gradient. Cells closest to the head end make lots of a chemical called retinoic acid, and those at the tail end make two other compounds, called FGF and Wnt. These diffuse along the body, such that different spots contain different amounts of the chemicals. So, for example, a cell thats closer to the head than the tail will know its position because its bathed in plenty of retinoic acid, but not so much Wnt or FGF.

Vertebrate segments arise from tissue called the mesoderm. Sandwiched between the cells that will make skin and those that will make most internal organs, the mesoderm will yield tissues such as bone and muscle.

As the embryo grows, part of the mesoderm tissue near the head begins to make its segments in the form of beads of tissue called somites, one on each side of the future spinal cord. They are squeezed out of that mesoderm like toothpaste from a tube, says Robb Krumlauf, a developmental biologist at the Stowers Institute for Medical Research in Kansas City, Missouri. These will turn into vertebrae and skeletal muscles. (Other body parts will develop from cells outside of the segments.)

If the segmentation process goes wrong, vertebrae can take the wrong shape: half-vertebrae, fused vertebrae or wedge-shaped ones, for example. In people, this causes a type of scoliosis, and also may affect the kidneys, heart and other body parts.

How does the embryo make just the right number of segments, all the right size? In the 1970s, English researchers came up with a model they called clock and wavefront. The embryos clock would tick to indicate each time a segment should be produced. The wavefront would consist of a maturation process traveling from head to tail, and cells at the crest of that maturation wave would be ready to segment. Whenever the clock ticked, they would spit out a new segment.

The developing mammalian embryo produces two somites, one each side of the future spinal canal, every time an internal clock ticks. The process is guided by a protein called FGF that is made by the tail end of the embryo and diffuses along its length, forming a gradient. Somite production occurs at a spot (the wave front) where the concentration of FGF is at just the right level when the clock makes a tick. The process repeats itself over and over, gradually building up segments, from which vertebrae and skeletal muscle are made. Two other molecules, Wnt and retinoic acid, also form gradients, and with FGF these are key to telling tissues where they are along an embryos length.

At that time, scientists had no idea what molecules would control either clock or wavefront, or if the theory was even correct. The first hard evidence for a clock came from experiments with chicken eggs, published in 1997.

Developmental biologist Olivier Pourqui, now at Harvard Medical School, was studying the chick version of a gene called hairy that is involved in segmentation in fruit flies. He and his colleagues saw the hairy gene turn on in a cyclical manner: starting out at the tail, and then closer to the head, every 90 minutes. And every 90 minutes, the embryo made a new segment.

That study confirmed that a ticking clock did underlie segmentation, says Michalis Averof, a comparative developmental biologist at CNRS in Lyon, France. In 2012, he reported a similar oscillator in beetles.

Scientists still dont know what sets that clocks pace, but they now know that a variety of other proteins, including two of those ruler proteins, Wnt and FGF (and another called Notch), turn on genes like hairy. The other part of the system the wavefront of maturation is characterized by concentrations of FGF. Since FGF is made at the tail end, levels of the protein will be highest there and lowest at the head. Cells that have a low enough level of FGF when the clock ticks will form a segment.

Changing the speed of the clock can have profound effects on the body plan, as Pourqui found in a 2008 study on snakes. Snakes have hundreds of vertebrae, compared to the few dozen in other vertebrates like chickens, mice and humans. How did this come to be? Compared with that of a mouse, their clock is accelerated, Pourqui found. The faster it ticks, the more segments get made, creating the snakes long spine. He doesnt yet know why the snake clock ticks faster, though.

The bone-and-muscle segments, and the rest of the embryos developing tissues, need instructions so that the ones near the front make shoulders and arms, the ones at the back end make hips and legs, and so on. This process, too, depends on the ruler laid down by retinoic acid, Wnt and FGF. The position of cells with respect to the ruler tells them which Hox genes to activate. The Hox genes then turn on other genes, to make the right size and shape of vertebrae, or a tail, arm, liver, etc.

Its complicated: Mammals have 39 different Hox genes, activated in different combinations along the body and with different parts to play. For example, mice usually grow a defined series of vertebrae, including 13 thoracic segments with ribs and six lumbar segments without. But when scientists bred mice to lack the Hox10 gene, the creatures grew little ribs on the lumbar segments. In rare cases in people, mutations in Hox genes cause diverse effects such as club foot, hair loss and extra fingers and toes.

Lewis, who worked with Hox mutant flies in the 1970s, also discovered a remarkable pattern to the Hox genes. In DNA, they are lined up in the same order in which they are produced, from head to tail, in the embryo. Genes at one end of the line spring into action in response to retinoic acid, with that signal emanating from the head; the other end responds to Wnt and FGF, signals from the rear.

A collection of genes called HOX are activated in different parts of an animals body plan, telling cells and tissues what to become. In the DNA, the genes line up in the same order as they are used in a developing embryo. There are remarkable similarities between the HOX genes of disparate creatures, such as fruit flies, mice and humans. In mammals, the HOX genes diversified so that there are four sets (HOX A, B, C and D) to the flys single set. Duplications also led to an expanded number of HOX genes in each set.

Much remains unknown about how bodies are arranged how the same set of Hox genes creates such different body plans in different animals, for example, and how the pace of the segmentation clock sets just right to make a spine to fit a snake or a mouse or a person. Studying such things in people, of course, is difficult. So Pourqui and colleagues recently turned to human stem cells in a dish.

Using genetic trickery, they engineered the cells to flash yellow every time a certain clock gene turned on. Watching for the yellow glow, the researchers detected a clock that had five hours between each tick. Pourqui now aims to figure out just what controls that five-hour timing.

Its astounding, Krumlauf says, how similar the parts of the body-plan system are across such a wide variety of organisms. Each animal uses many of the same genetic tools, in different ways, to create its own unique shape.

In that respect, then, its not so surprising that Jeff Goldblums character melded so completely with a fly. Wnt, FGF, Hox genes its how we apply them that makes us the creatures we are.

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How do bodies position arms, legs, wings and organs? - Knowable Magazine

Spinal Cord Stem Cells Comments Off on How do bodies position arms, legs, wings and organs? – Knowable Magazine | January 30th, 2020

GIOSTAR/HEAMGEN has developed and secured patented technology to manufacture lifesaving mature red blood cells from stem cells. The red blood cells are made utilizing a bioreactor that permits the production of mature red blood cells, under strictly controlled conditions, for transfusion therapy and replaces the need for a human blood donor. GIOSTAR/HEAMGEN mature red blood cells are safe and not compromised by inadequate pathogen detection and inactivation of diseases such as hepatitis C, HIV, hepatitis B and syphilis. The red blood cells are O-Negative (Universal Donor) to eliminate incompatibility and allosensitization reactions.

ATLANTA (PRWEB) January 29, 2020

GIOSTAR/HEAMGEN has developed and secured patented technology to manufacture lifesaving mature red blood cells from stem cells. The red blood cells are made utilizing a bioreactor that permits the production of mature red blood cells, under strictly controlled conditions, for transfusion therapy and replaces the need for a human blood donor. GIOSTAR/HEAMGEN mature red blood cells are safe and not compromised by inadequate pathogen detection and inactivation of diseases such as hepatitis C, HIV, hepatitis B and syphilis. The red blood cells are O-Negative (Universal Donor) to eliminate incompatibility and allosensitization reactions. Trauma situations often do not allow for adequate blood typing due to time restrictions, so the GIOSTAR/HEAMGEN red blood cells address that need effectively.

"There are three main problems for blood transfusions," stated Dr. Anand Srivastava, Founder and Chairman of GIOSTAR. "First we have to match the blood type. Second, there's not enough blood available every single time. And third, when we transfer blood from one person to another person, there is always a chance of the transfer of disease."

Watch a feature interview with Dr. Anand Srivastava on The DM Zone with host Dianemarie Collins.

The World Health Organization (WHO) published the first detailed analysis on the global supply and demand for blood in October 2019 and found that 119 out of 195 countries do NOT have enough blood in their blood banks to meet hospital needs. In those nations, which include every country in central, eastern, and western sub-Saharan Africa, Oceania (not including Australasia), and south Asia are missing roughly 102,359,632 units of blood, according to World Health Organization (WHO) goals. While total blood supply around the world was estimated to be around 272 million units, in 2017, demand reached 303 million units. That means the world was lacking 30 million units of blood, and in the 119 countries with insufficient supply, that shortfall reached 100 million units.

The global market opportunity for GIOSTAR/HEAMGEN technology presents not only a profitable and scalable business opportunity but also a significant social and environmental impact. The global market is estimated to be at least $ 85 Billion/year.

GIOSTAR/HEAMGEN has identified early entry global markets to include Military, Trauma, Asia (replace Hepatitis C contaminated blood products), Africa (AIDS contaminated blood), Newborns, Thalassemia patients, Allosensitized sickle cell disease patients. South Sudan was found to have the lowest supply of blood, at 46 units per 100,000 people. In fact, the country's need for blood was deemed 75 times greater than its supply. In India, which had the largest absolute shortage, there was a shortfall of nearly 41 million units, with demand outstripping supply by over 400 percent. Strategic investments are needed in many low-income and middle-income countries to expand national transfusion services and blood management systems. Oncology is a major user of blood transfusion but if countries don't have the capacity to manage the bulk of oncology, it will limit complex surgery options.

GIOSTAR/HEAMGEN has acquired the exclusive license to the patent for the technique for stem cell proliferation from University of California San Diego (UCSD). The founding team of GIOSTAR/HEAMGEN is comprised of the scientists and clinicians who were involved in creating the Intellectual Property at UCSD and has already achieved PROOF OF CONCEPT - the optimized lab scale proliferation of mature red blood cells - at UCSD as part of their research.

GIOSTAR/HEAMGEN is currently looking for strategic partnerships (Contact Doug@DMProductionsLLC.com) to accelerate the development of donor-independent red blood cells manufacturing capabilities and advance the proof of concept work already done (patented) around the manufacture of safe, universal donor, human red blood cells. GIOSTAR/HEAMGEN will also develop a full automated proprietary bioreactor using robotic technology to produce abundant quantities of red blood cells with a goal for cost-effective commercialization of fresh, human, universal donor Red Blood Cells (RBCs).

ABOUT GIOSTAR

Dr. Anand Srivastava is a Chairman and Cofounder of California based Global Institute of Stem Cell Therapy and Research (GIOSTAR) headquartered in San Diego, California, (U.S.A.). The company was formed with the vision to provide stem cell based therapy to aid those suffering from degenerative or genetic diseases around the world such as Parkinson's, Alzheimer's, Autism, Diabetes, Heart Disease, Stroke, Spinal Cord Injuries, Paralysis, Blood Related Diseases, Cancer and Burns. GIOSTAR is a leader in developing most advance stem cell based technology, supported by leading scientists with the pioneering publications in the area of stem cell biology. Company's primary focus is to discover and develop a cure for human diseases with the state of the art unique stem cell based therapies and products. The Regenerative Medicine provides promise for treatments of diseases previously regarded as incurable.

GIOSTAR is world's leading Stem cell research company involved with stem cell research work for over a decade. It is headed by Dr Anand Srivastava, who is a pioneer and a world-renowned authority in the field of Stem Cell Biology, Cancer and Gene therapy. Several governments and organizations including USA, India, China, Turkey, Kuwait, Thailand, Philippines, Bahamas, Saudi Arabia and many others seek his advice and guidance on drafting their strategic and national policy formulations and program directions in the area of stem cell research, development and its regulations. Under his creative leadership, a group of esteemed scientists and clinicians have developed and established Stem Cell Therapy for various types of autoimmune diseases and blood disorders, which are being offered to patients in USA and soon it will be offered on a regular clinical basis to the people around the globe.

For the original version on PRWeb visit: https://www.prweb.com/releases/giostar_announces_medical_breakthrough_in_biotechnology_and_lifesciences_to_manufacture_abundant_safe_red_blood_cells_from_stem_cells/prweb16854975.htm

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GIOSTAR Announces Medical Breakthrough in Biotechnology and Lifesciences To Manufacture Abundant, Safe Red Blood Cells From Stem Cells - Benzinga

Spinal Cord Stem Cells Comments Off on GIOSTAR Announces Medical Breakthrough in Biotechnology and Lifesciences To Manufacture Abundant, Safe Red Blood Cells From Stem Cells – Benzinga | January 30th, 2020

CHICAGO - Brian Wallach wasn't supposed to live to see his younger daughter's first birthday.

Diagnosed with amyotrophic lateral sclerosis (ALS), a terminal disease with no cure, doctors told him in 2017 that he might have six months to live.

Today, he's focused on being there for his daughter's future firsts: kindergarten drop-off, middle school dance, wedding day.

More than two years after his diagnosis, he has been lucky, he said, to experience relatively limited progression of his disease. After some balance issues, the Kenilworth resident now uses a cane - or, as he is careful to specify, a "cool walking stick" - to get around.

When Wallach was diagnosed, neither he nor his wife, Sandra Abrevaya, knew much about ALS, a neurodegenerative disease that affects nerve cells in the brain and the spinal cord, eventually paralyzing even the body's ability to breathe.

In response to Wallach's diagnosis, the couple, both 39, launched I AM ALS in 2019. Former staffers in the Obama White House, they marshaled lessons learned while campaigning - gathering information, forming consensus, considering the impossible possible - to build a force to mobilize hope and change for those facing a disease they say can and should be cured.

Rays of hope are beginning to emerge through an innovative trial that received FDA approval last week to test several drugs at the same time, a bipartisan congressional caucus, doubled federal funding, and support from groups like the Chan Zuckerberg Initiative, which gave the couple's organization a $453,000 grant in September.

"Last year we made hope a word that was OK to use," Wallach said. "This year we have to make hope real."

Audaciousness is the only option, the couple says, in their race against the clock.

Wallach logged 120,000 miles in the air last year, including traveling to Washington, D.C., in April, where he testified before Congress and asked legislators to amp up funding.

"Last year, every time someone said, 'Do you want to speak to us,' I said, 'yes.' Every time someone said, 'There's a meeting,' I said, 'I'm going.'" he said. "Every time there was anything, I said, 'Great, I'm on the plane.'"

Until October, when Wallach fell while exiting a Lyft in Boston after swinging a heavy backpack onto his back. Thirteen staples in his head later, and after terrifying Abrevaya with a phone call, the two agreed he wouldn't travel alone anymore. He's maintaining momentum for the cause with more hours in his home office and fewer in airports.

In December, I AM ALS debuted billboards around Times Square as part of its #CuresForAll campaign aimed at informing the public about the impact a cure or better treatment for a neurodegenerative disease can have on other diseases such as multiple sclerosis, Alzheimer's and Parkinson's. ALS patients and their families from states including Michigan, Maine and Colorado were in New York for the launch.

The billboards noted the number of people lost to ALS each day - 16 - with photographs of those who died in 2019. Days earlier, Pete Frates, a founder of the viral fundraiser the Ice Bucket Challenge, which raised $115 million, had died. He was 34.

The campaign was also shared on social media. The posts expressed the suffering and loss nationwide: a mother wrote about her son who was diagnosed at 20 and died at 28; a son posted in honor of his dad; Colorado Rep. Jason Crow posted a message honoring his cousin.

It's time, the couple said, to switch ALS conversations from a diagnosis rooted in darkness to the faces of people bravely moving forward. They want to speed development of potential cures and give patients more access to experimental treatments.

That's not an unreasonable goal, said Sabrina Paganoni, a faculty member at The Sean M. Healey & AMG Center for ALS at Mass General in Boston, which plans to test at least five different medications for ALS at the same time, a first for the disease and something she said could be a huge turning point.

On Wednesday, the Healey Center announced it received FDA approval to move forward with testing the first three drugs: Zilucoplan, Verdiperstat and CNM-Au8. Similar to how cancer drugs are already tested, this gives patients access to more treatments and allows researchers to quickly collect data and accelerate the pace toward a cure.

"This is a very exciting time in the history of ALS," Paganoni said. "I think this is going to be the decade when ALS is changed from a rapidly fatal disease to a more chronic disease that we can manage."

For years, Steve Perrin, the chief executive officer at the ALS Therapy Development Institute, has monitored clinical trials for ALS. So far, he said, the two drugs approved by the FDA, Radicava and Rilutek, are "a very marginal slowing down of disease."

This year, he said the quality of drugs going into trials seems improved. He is excited about several trials, including one studying stem cells and another testing a drug to potentially slow progression in some patients.

"As a patient you want to see something measurable, and I don't mean measurable in days," he said. "If I'm a patient, I want to see something, and I want hope for myself and my family. I want something that is going to slow the disease down so I can watch my kids growing up, I can watch them graduate from college, I can watch them marry."

But that takes resources.

"We are in a time when we can reasonably say that there's going to be new treatments available," Paganoni said. "But we need more funding and support, so all of this can happen, and happen soon."

Nearly every moment feels like a push-pull for Wallach and Abrevaya.

Do they spend more precious minutes with their two daughters, ages 4 and 2, or do they spend time away, among strangers - on a plane, in a researcher's office, walking the halls of Congress - with the hope that those minutes will, someday, result in time banked to create more family memories.

"The hardest balance, if I'm honest, is, I love every minute I have with them," Wallach said about his daughters, "but I also feel this pressing sense of, I need to be working towards a goal of actually finding a cure."

"We're doing that so we have a shot at a real future together," Abrevaya said about their time spent traveling and advocating.

At home, when the family heads for the door, the toddlers reach for their father's shoes, and they get his walking stick.

"While that both fills your heart with joy and appreciation, it's also painful that your toddlers are being put in this position," Abrevaya said.

The parents guard normalcy. They take their daughters to swim at the neighborhood pool and on vacation with friends. Wallach wishes he could lift them above his head to touch the ceiling, like their uncle can. But he can lie on the floor and play with them; he can listen to them belt out songs on their purple karaoke machine.

They find ways to lighten a heavy subject. On New Year's Eve, the two danced in a video on the foundation's Instagram, singing into hairbrushes, and Wallach promised to get an "ALS: You Gone" tattoo if 20,000 people donated $10 to a Healey Center research fundraiser. It raised $40,000 in 24 hours, Wallach said. No matter the outcome, he plans to get the tattoo.

The couple, who both work full-time jobs - Abrevaya is the president of nonprofit Thrive, Wallach works at law firm Skadden, Arps, Slate, Meagher & Flom - want more research, to create a patient navigation system, and to gather signatures for a letter asking new FDA commissioner Stephen Hahn to speed ALS patients' access to possible treatments.

And they keep looking for light. But it takes work.

Changing life with ALS for Wallach, and for other patients and their families, requires bold action from people with the power to make change: politicians, researchers, philanthropists.

As they meet others with ALS, they welcome new friends and face the pain of losing some.

"It does make you uniquely urgent in what you do," Wallach said. "You push because you have to. You push because you know that the time that we have is precious, and that you want to see 20 years from now. And know that you can make that happen."

Wallach often shares moments about his ALS journey on Twitter with his 40,000 followers. Recently, he shared something he wasn't sure he should. It was a time he was unable to find light.

On a recent night, he woke up to pain he's had for the past few months, radiating from his right hip to his right calf.

He clutched a stuffed llama his daughter gave him. And he began to cry.

"I cried because of the pain. I cried because I couldn't be the father to my girls I dreamed of being," he wrote. "I cried because I couldn't be the husband to my wife I dream of being. Because I saw the future zooming ahead, and for a brief moment I wondered if I would be a part of it."

His wife heard him crying that night. She asked what was wrong. And he said maybe they would be better off if he left, living instead in an assisted living facility. Their daughters, he told her, could have a dad who could do everything he dreamed of doing.

She looked at him in the dark. "You are my light," she said. "You are their light. The only way you are leaving us is if you die in my arms, and we aren't going to let that happen for a long, long, long time."

Distributed by Tribune Content Agency, LLC.

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In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later - PostBulletin.com

Spinal Cord Stem Cells Comments Off on In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later – PostBulletin.com | January 27th, 2020

CHICAGO Brian Wallach wasnt supposed to live to see his younger daughters first birthday.

Diagnosed with amyotrophic lateral sclerosis (ALS), a terminal disease with no cure, doctors told him in 2017 that he might have six months to live.

Today, hes focused on being there for his daughters future firsts: kindergarten drop-off, middle school dance, wedding day.

More than two years after his diagnosis, he has been lucky, he said, to experience relatively limited progression of his disease. After some balance issues, the Kenilworth resident now uses a cane or, as he is careful to specify, a cool walking stick to get around.

When Wallach was diagnosed, neither he nor his wife, Sandra Abrevaya, knew much about ALS, a neurodegenerative disease that affects nerve cells in the brain and the spinal cord, eventually paralyzing even the bodys ability to breathe.

In response to Wallachs diagnosis, the couple, both 39, launched I AM ALS in 2019. Former staffers in the Obama White House, they marshaled lessons learned while campaigning gathering information, forming consensus, considering the impossible possible to build a force to mobilize hope and change for those facing a disease they say can and should be cured.

Rays of hope are beginning to emerge through an innovative trial that received FDA approval last week to test several drugs at the same time, a bipartisan congressional caucus, doubled federal funding, and support from groups like the Chan Zuckerberg Initiative, which gave the couples organization a $453,000 grant in September.

Last year we made hope a word that was OK to use, Wallach said. This year we have to make hope real.

Audaciousness is the only option, the couple says, in their race against the clock.

Wallach logged 120,000 miles in the air last year, including traveling to Washington, D.C., in April, where he testified before Congress and asked legislators to amp up funding.

Last year, every time someone said, Do you want to speak to us, I said, yes. Every time someone said, Theres a meeting, I said, Im going. he said. Every time there was anything, I said, Great, Im on the plane.

Until October, when Wallach fell while exiting a Lyft in Boston after swinging a heavy backpack onto his back. Thirteen staples in his head later, and after terrifying Abrevaya with a phone call, the two agreed he wouldnt travel alone anymore. Hes maintaining momentum for the cause with more hours in his home office and fewer in airports.

In December, I AM ALS debuted billboards around Times Square as part of its #CuresForAll campaign aimed at informing the public about the impact a cure or better treatment for a neurodegenerative disease can have on other diseases such as multiple sclerosis, Alzheimers and Parkinsons. ALS patients and their families from states including Michigan, Maine and Colorado were in New York for the launch.

The billboards noted the number of people lost to ALS each day 16 with photographs of those who died in 2019. Days earlier, Pete Frates, a founder of the viral fundraiser the Ice Bucket Challenge, which raised $115 million, had died. He was 34.

The campaign was also shared on social media. The posts expressed the suffering and loss nationwide: a mother wrote about her son who was diagnosed at 20 and died at 28; a son posted in honor of his dad; Colorado Rep. Jason Crow posted a message honoring his cousin.

Its time, the couple said, to switch ALS conversations from a diagnosis rooted in darkness to the faces of people bravely moving forward. They want to speed development of potential cures and give patients more access to experimental treatments.

Thats not an unreasonable goal, said Sabrina Paganoni, a faculty member at The Sean M. Healey & AMG Center for ALS at Mass General in Boston, which plans to test at least five different medications for ALS at the same time, a first for the disease and something she said could be a huge turning point.

On Wednesday, the Healey Center announced it received FDA approval to move forward with testing the first three drugs: Zilucoplan, Verdiperstat and CNM-Au8. Similar to how cancer drugs are already tested, this gives patients access to more treatments and allows researchers to quickly collect data and accelerate the pace toward a cure.

This is a very exciting time in the history of ALS, Paganoni said. I think this is going to be the decade when ALS is changed from a rapidly fatal disease to a more chronic disease that we can manage.

For years, Steve Perrin, the chief executive officer at the ALS Therapy Development Institute, has monitored clinical trials for ALS. So far, he said, the two drugs approved by the FDA, Radicava and Rilutek, are a very marginal slowing down of disease.

This year, he said the quality of drugs going into trials seems improved. He is excited about several trials, including one studying stem cells and another testing a drug to potentially slow progression in some patients.

As a patient you want to see something measurable, and I dont mean measurable in days, he said. If Im a patient, I want to see something, and I want hope for myself and my family. I want something that is going to slow the disease down so I can watch my kids growing up, I can watch them graduate from college, I can watch them marry.

But that takes resources.

We are in a time when we can reasonably say that theres going to be new treatments available, Paganoni said. But we need more funding and support, so all of this can happen, and happen soon.

Nearly every moment feels like a push-pull for Wallach and Abrevaya.

Do they spend more precious minutes with their two daughters, ages 4 and 2, or do they spend time away, among strangers on a plane, in a researchers office, walking the halls of Congress with the hope that those minutes will, someday, result in time banked to create more family memories.

The hardest balance, if Im honest, is, I love every minute I have with them, Wallach said about his daughters, but I also feel this pressing sense of, I need to be working towards a goal of actually finding a cure.

Were doing that so we have a shot at a real future together, Abrevaya said about their time spent traveling and advocating.

At home, when the family heads for the door, the toddlers reach for their fathers shoes, and they get his walking stick.

While that both fills your heart with joy and appreciation, its also painful that your toddlers are being put in this position, Abrevaya said.

The parents guard normalcy. They take their daughters to swim at the neighborhood pool and on vacation with friends. Wallach wishes he could lift them above his head to touch the ceiling, like their uncle can. But he can lie on the floor and play with them; he can listen to them belt out songs on their purple karaoke machine.

They find ways to lighten a heavy subject. On New Years Eve, the two danced in a video on the foundations Instagram, singing into hairbrushes, and Wallach promised to get an ALS: You Gone tattoo if 20,000 people donated $10 to a Healey Center research fundraiser. It raised $40,000 in 24 hours, Wallach said. No matter the outcome, he plans to get the tattoo.

The couple, who both work full-time jobs Abrevaya is the president of nonprofit Thrive, Wallach works at law firm Skadden, Arps, Slate, Meagher & Flom want more research, to create a patient navigation system, and to gather signatures for a letter asking new FDA commissioner Stephen Hahn to speed ALS patients access to possible treatments.

And they keep looking for light. But it takes work.

Changing life with ALS for Wallach, and for other patients and their families, requires bold action from people with the power to make change: politicians, researchers, philanthropists.

As they meet others with ALS, they welcome new friends and face the pain of losing some.

It does make you uniquely urgent in what you do, Wallach said. You push because you have to. You push because you know that the time that we have is precious, and that you want to see 20 years from now. And know that you can make that happen.

(EDITORS: STORY CAN END HERE)

Wallach often shares moments about his ALS journey on Twitter with his 40,000 followers. Recently, he shared something he wasnt sure he should. It was a time he was unable to find light.

On a recent night, he woke up to pain hes had for the past few months, radiating from his right hip to his right calf.

He clutched a stuffed llama his daughter gave him. And he began to cry.

I cried because of the pain. I cried because I couldnt be the father to my girls I dreamed of being, he wrote. I cried because I couldnt be the husband to my wife I dream of being. Because I saw the future zooming ahead, and for a brief moment I wondered if I would be a part of it.

His wife heard him crying that night. She asked what was wrong. And he said maybe they would be better off if he left, living instead in an assisted living facility. Their daughters, he told her, could have a dad who could do everything he dreamed of doing.

She looked at him in the dark. You are my light, she said. You are their light. The only way you are leaving us is if you die in my arms, and we arent going to let that happen for a long, long, long time.

Finally, he smiled.

2020 Chicago Tribune

Visit the Chicago Tribune at http://www.chicagotribune.com

Distributed by Tribune Content Agency, LLC.

PHOTOS (for help with images, contact 312-222-4194): ALS-BATTLE

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In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later - Bryan-College Station Eagle

Spinal Cord Stem Cells Comments Off on In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later – Bryan-College Station Eagle | January 26th, 2020

Researchers at Karolinska Institutet in Sweden have revealed a new principle of organisation which explains how locomotion is coordinated in vertebrates akin to an engine with three gears. The results are published in the scientific journal Neuron.

A remarkable feature of locomotion is its capacity for rapid starts and to change speed to match our intentions. However, there is still uncertainty as to how the rhythm-generating circuit - the locomotor engine - in the spinal cord is capable of instantaneously translating brain commands into rhythmic and appropriately paced locomotion.

Using zebrafish as a model organism, researchers at Karolinska Institutet reveal in detail a full reconstruction of the rhythm-generating engine driving locomotion in vertebrates.

"We have uncovered a novel principle of organisation that is crucial to perform an intuitively simple, yet poorly understood function: the initiation of locomotion and the changing of speed," says Abdel El Manira, Professor at the Department of Neuroscience at Karolinska Institutet, who led the study.

The researchers performed a comprehensive and quantitative mapping of connections (synapses) between neurons combined with behavioural analyses in zebrafish. The results revealed that the excitatory neurons in the spinal cord which drive locomotion form three recurrent, rhythm-generating circuit modules acting as gears which can be engaged at slow, intermediate or fast locomotor speeds. These circuits convert signals from the brain into coordinated locomotor movements, with a speed that is aligned to the initial intention.

"The insights gained in our study can be directly applicable to mammals, including humans, given that the organising principle of the brainstem and spinal circuits is shared across vertebrate species," says Abdel El Manira. "Understanding how circuits in the brainstem and spinal cord initiate movements and how speed is controlled will open up for new research avenues aimed at developing therapeutic strategies for human neurological disorders, including traumatic spinal cord injury, and motoneuron degenerative diseases such as amyotrophic lateral sclerosis (ALS)."

Reference: Song, J., Pallucchi, I., Ausborn, J., Ampatzis, K., Bertuzzi, M., Fontanel, P., Picton, L. D., & Manira, A. E. (2020). Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2019.12.030

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The Spinal Cord Organizes Locomotion Like a Three-gear Engine - Technology Networks

Spinal Cord Stem Cells Comments Off on The Spinal Cord Organizes Locomotion Like a Three-gear Engine – Technology Networks | January 23rd, 2020

A small injury to a nerve outside the brain and spinal cord is relatively easy to repair just by stretching it, but a major gap in such a peripheral nerve poses problems. Usually, another nerve is taken from elsewhere in the body, and it causes an extra injury and returns only limited movement.

Now researchers at the University of Pittsburgh have found an effective way to bridge such a gapat least in mice and monkeysby inserting a biodegradable tube that releases a protein called a growth factor for several months. In a study published Wednesday in Science Translational Medicine, the team showed that the tube works as a guide for the nerve to grow along the proper path, and the naturally occurring protein induces the nerve to grow faster.

Kacey Marra, a professor at the universitys departments of plastic surgery and bioengineering, says shes been working for a dozen years on the device, which she particularly hopes will help soldiers injured in combat. More than half of injured soldiers suffer nerve injuries, she says. And as the daughter and granddaughter of military men, she considers it her mission to help their successors. Combat gear does a good job of protecting a soldiers chest and head, but arms and legs are often exposed, which is why peripheral nerve injuries are so common, Marra says. Car crashes and accidents involving machinery such as snowblowers can also damage nerves involved in hand, arm, leg and foot control.

In the U.S., there are about 600,000 nerve injuries every year, she says, though she is unsure how many are severe enough to require the relocation of a second nerve because that information is not tracked yet. When the injuries are severe, the only current treatment is to take a nerve from somewhere else on the body, Marra says. But patients recover just about 50 to 60 percent of function in the damaged nerve.

Longer nerve grafts are always more challenging, says Christine Schmidt, a professor and chair of the department of biomedical engineering at the University of Florida, who was not involved with the research. It would be great to be able to tackle long-term nerve damage. She notes that the nerve the Pittsburgh team tested is relatively small in macaques. It will still be a challenge to scale up to larger nerves, she says. It would be nice to see a little bit larger nerve, which would be more relevant to patients.

The new device restored nearly 80 percent of function, the study showed. It uses glial-cell-derived neurotrophic factor (GDNF), a protein that promotes nerve cell survival. Marra chose GDNF, she says, because if you get a nerve injury like a paper cut, the cells in your nerves are going to express this protein at high levels. And that recruits other cells to come in and repair the nerve. The tube is made of the same polymer as dissolvable stitches, which has already been federally approved for surgical use.

Other researchers are exploring the use of stem cells or other cells to help bridge the gap in the nerve, but Marra and her colleagues approach is likely to have an easier time receiving federal approval because it does not involve cells. If they were to go adding stem cells or too many complexities, it would be harder to win a regulatory green light, Schmidt says. It is better to make advances with small steps, as the Pittsburgh researchers have, she says. Theyre doing it in a very realistic way that can lead to a clinical outcome, and thats really what you want, Schmidt adds.

Nerves can regenerate at a rate of about one millimeter per day, and there are three months worth of GDNF in the tube, allowing for closing injuries of about 12 centimetersor 4.7 inches.

In the eight-year-long study, the researchers trained rhesus macaques to eat with their forefinger and thumbwhich they could only do if a repaired nerve was working properly. They used this finger maneuver rather than grabbing food with their fist, as they usually do when they eat. If they pinched the banana pellet, they got a second treat, Marra says. We were able to see the recovery, she adds. At that point, we knew we were ready to test in humans.

Marra says she and her colleagues have several pending proposals for the first clinical trials in humans, which are likely to start in 2021 and take at least three years. A start-up she launched, AxoMax Technologies, licensed the technology from the University of Pittsburgh to begin the experiments. Marra believes her device can be competitively priced, compared with moving a nerve from elsewhere in the bodyand, potentially, even compared with existing repair approaches for small nerve gaps.

Her team is also beginning to study whether its method will work for facial nerves, but she thinks it is unlikely to be effective for spinal cord injuries, which are far more complex and involve more nerves. The researchers are looking at regenerating the muscles affected by injured nerves as well. I think [this approach] really could revolutionize thinking about nerve repair and the different options a patient will have, Marra says.

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New Nerve-Growing Method Could Help Injured Soldiers and Others - Scientific American

Spinal Cord Stem Cells Comments Off on New Nerve-Growing Method Could Help Injured Soldiers and Others – Scientific American | January 23rd, 2020

Automobile Antenna Market Overview Forecast To 2028

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To analyze and forecast the market size of Automobile AntennaIndustry in theglobal market. To study the global key players, SWOT analysis, value and global market share for leading players. To determine, explain and forecast the market by type, end use, and region. To analyze the market potential and advantage, opportunity and challenge, restraints and risks of global key regions. To find out significant trends and factors driving or restraining the market growth. To analyze the opportunities in the market for stakeholders by identifying the high growth segments. To critically analyze each submarket in terms of individual growth trend and their contribution to the market. To understand competitive developments such as agreements, expansions, new product launches, and possessions in the market. To strategically outline the key players and comprehensively analyze their growth strategies.

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The growth of this market globally is subjected to various factors, including consumer ace Automobile Antennaof a lot of Automobile Antennaproducts, inorganic company growth models, price volatility of raw materials, product innovation along with economic prospects in both producer and consumer countries.

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Cell Processing Technologies Market Advance Technology And New Innovations By 2027 Illuminated By New Report - Melanian News

Spinal Cord Stem Cells Comments Off on Cell Processing Technologies Market Advance Technology And New Innovations By 2027 Illuminated By New Report – Melanian News | January 22nd, 2020

The first squeeze of my left thumb is gentle, almost reassuring. I rate it as 0 out of 100 on the pain scale.

But as a technician ramps up pressure on the custom-made thumb-squeezing device, it becomes less pleasant. I give ratings of 2, 6 then 36. A few squeezes later, Im at 79.

At 84, Im glad the test is over as I put my tender thumb to my lips.

Ive offered myself up for a pain study at the University of Michigan, in a long, low-slung building northeast of the universitys main campus in Ann Arbor. As the day wears on, Ill undergo needle pokes, leg squeezes and an MRI scan all part of a grand bid tobetter understand the root cause of an individuals pain, and point to the best solutions.

Its an understanding thats sorely needed. Lucky for me, Im just a control in this experiment, and I can cry for mercy whenever I want. Thats not the case for the multitudes of people 50 million in the US alone who have ongoing, chronic pain, for whom the medical pause buttons are far from adequate.

The thumb pressure test, in which participants rate their pain level on a scale from 0 to 100 as their thumbs are subjected to increasing pressure, is one of several ways that clinicians and researchers can evaluate a persons pain responses. Since peoples thresholds to pain in tests like this vary according to pain syndrome, such tests can help with diagnosis. (Credit: Amber Dance)

Our treatments for chronic pain are very bad, says Richard E. Harris, a neuroscientist at the University of Michigans Chronic Pain and Fatigue Research Center and a co-researcher on the study, which should ultimately help to improve diagnoses and therapies. Today, doctors mostly define pain by where it is: the abdomen, the lower back, the joints. Then they offer up treatments, usually anti-inflammatories or opioids, that too often do nothing to the cells and molecules causing a person to hurt. A recent analysis in theJournal of the American Medical Associationfound thatopioids reduced pain by an average of less than one point on a 10-point scale, across a variety of chronic conditions.

As part of the precision medicine movement and thanks to modern brain-imaging technology, scientists are starting to puzzle out the different types of pain: what causes them, how to diagnose them and how to prescribe treatments to match. Its an area that is far from settled. As recently as 2017, the International Association for the Study of Pain defineda new pain type, called nociplastic. Its characterized by the absence of any nerve or tissue damage in the parts that hurt.

Dan Clauw, director of the Michigan pain center, is passionate about helping people with this kind of long-misunderstood pain, which could underpin chronic conditions, such as fibromyalgia, that afflict millions. His blue eyes flash behind spectacles as he describes crisscrossing the globe to educate other physicians about nociplastic pain. Hes wearing a navy blazer and slacks when we meet for lunch between my testing sessions, because hes just returned from giving a presentation about marijuana and pain. He jokes that his colleagues wont recognize him out of his usual jeans.

Imaging the brain, along with doing prodding and poking tests of the type I endured, is beginning to point to signatures that explain the problem and suggest solutions. Eventually, this knowledge will help scientists to develop more targeted therapies, so doctors can treat patients better.

In broad strokes, pain falls into three categories: nociceptive, neuropathic and nociplastic. (Noci- is from the Latin for to do harm.)

Nociceptive pain results from inflammation or direct damage to tissues. When thattorture devicesqueezes my thumb, for example, pain-sensing nerves notice the pressure and spring into action. They transmit messages to my spinal cord, which sends them on to my brain, telling me Ouch!

This kind of discomfort is often short-lived; mine dissipates after Ive sucked on my thumb for a few moments. Nociceptive pain can also be chronic, though for example in osteoarthritis, where the cartilage in joints wears away and causes stretching of tendons and ligaments, or through the ongoing inflammation of rheumatoid arthritis.

Neuropathic pain, in contrast, happens when the pain-sensing nerves themselves are damaged or irritated, so that they send inappropriate Ow! signals to the brain. It typically results from some injury or disease, such as diabetes or shingles. It can also happen when a nerve is pinched, as in the case of carpal tunnel syndrome, when a nerve in the wrist gets squeezed. Its often long-lasting, unless the damage is repaired.

And nociplastic, the newly named type, results from no obvious inflammation or injury. Rather, its as if the volume knob for pain is turned up way too high, not at the pain site itself but further afield. Nociplastic pain seems to arise in parts of the central nervous system the brain or spinal cord that receive, transmit or process those Ouch! signals. These nerves misfire, creating a sensation of pain even though nothing may be wrong. The location of the problem, the central nervous system, is why Clauw prefers to call it central sensitization. The classic example is fibromyalgia, which causes pain that seems to stem from muscles, tendons and joints, despite the real problems lying in the brain or spinal cord.

Scientists understanding of pain continues to evolve and so do the various terms used to describe it. Ideally, definitions are standardized and reflect the biology underpinning the pain, but the lack of straightforward tests for parsing types of pain makes defining it a challenge. Nociceptive pain involves pain-sensing nerves called nociceptors, which also can be involved in neuropathic pain. A third pain type is believed to arise wholly in the central nervous system. But there can be overlap: Nociceptive and neuropathic pain can, over time, lead to central nervous system-generated pain.

Complicating the picture, a person might have more than one type of pain going on at the same time. In 2012, the journalPainpublished a case report of a person with burning, prickling pain on both sides of the body. Treatment with pregabalin, an epilepsy medication that can also address neuropathic pain and central sensitization,relieved pain on the right side of the body, but not the left.

All this pain classifying is more than an academic exercise: It should help guide how to treat people. For example, consider a patient with knee pain. If the issue is nociceptive, anti-inflammatories or knee surgery should help. But if the problem is central, those treatments probably wont make much difference. A better bet would be medications that can directly influence the misfiring central nervous system. Some antidepressants, for example, act on the brains chemical messengers neurotransmitters that are involved in pain, altering their signaling to quell the Ouch message.

Non-drug treatments such as acupuncture and cognitive behavioral therapy also may help because they influence how the brain perceives pain. Acupunctureboosts availability of brain receptors that respond to the bodys natural painkillers. A recent analysis inJAMA Internal Medicineof more than 6,000 people taking opioids found that treatments such as meditation, hypnosis and cognitive behavioral therapyreduced pain and diminished the drug doses needed to control it.

Though the term nociplastic is new, Clifford Woolf, a neurobiologist at Boston Childrens Hospital and Harvard Medical School,first proposed the concept in 1983. Yet the idea has been slow to catch on. In the 1990s, when Clauw began studying fibromyalgia, it was a disease so vague, so puzzling, that some physicians simply denied its existence.

Today, fibromyalgia is more likely to be accepted as a real condition. But many doctors still dont appreciate how centralized problems might underlie pain even when the symptoms look nociceptive or neuropathic, Clauw says. The distinctions between pain types are not clean: If left untreated, nociceptive pain may sensitize the nervous system, turning a temporary problem into chronic, nociplastic pain, for example. Clauw and his Michigan colleagues believe that central sensitization shows up in myriad conditions, from irritable bowel syndrome to chronic pelvic pain to dry eye disease. And in the study Ive signed up for, they want to clarify how often this happens and how doctors might detect it in patients who show up begging for pain relief.

To that end, the team has enrolled people with three different pain disorders that seem, on the surface, to be nociceptive or neuropathic. The scientists will test their pain before and after standard treatments. If the pain is in fact central, the treatments shouldnt work a disappointment for the participants, but one that might eventually lead to better understanding and treatment for them and others like them.

Two categories of subjects have what looks like nociceptive pain: those with osteoarthritis of the hip, who will receive a hip replacement, and those with inflammatory rheumatoid arthritis, who will be treated with modern medications. A third group, people with carpal tunnel syndrome, represent neuropathic pain and will get surgery to receive the pressure on the nerve.

But if Clauw and his crew are right, then some of these people will really be suffering from central sensitization, instead of or in addition to the nociceptive or neuropathic problem. Two control groups will help tease that out: People with fibromyalgia will show the researchers what pure central sensitization looks like, and those like me, with no chronic pain, will represent the non-central state.

The primary way that physicians measure pain today is to ask someone how much theyre hurting. Identification of biomarkers from, for example, brain imaging or blood tests could provide more objective measures of pain that would offer benefits in a variety of settings.

Once all the data are in, the researchers hope that pain features shared by the people with fibromyalgia and the others whose treatments dont work will reveal a potential signature for central sensitization.

The challenge is that theres no simple blood test or X-ray that will distinguish one type of pain from another. Theres no single measure that, by itself, will represent pain, says Woolf, author of a paper in theAnnual Review of Neuroscienceabout pain caused by problems in the sensory machinery. We need a composite.

To build that composite, scientists must resort to a variety of indirect measures, including responses to the pokes and prods being inflicted on me and other subjects.

This particular piece of the picture, called quantitative sensory testing or QST, measures the threshold at which a person can feel a given sensation such as pressure, heat or cold and when that sensation becomes painful. This can reveal how a persons nervous system deals with pain, and how that system might be off-kilter. Specific defects in nerves lead to specific changes in pain responses, helping scientists to distinguish one pain type from another.

Its simple, but revealing. For example, in the case of the thumb-press test, a person with fibromyalgia would probably start to feel pain at around four pounds of pressure. Clauw, who has no chronic pain of any stripe and is relatively pain-insensitive, says that he can handle up to about 18 pounds of pressure before it becomes uncomfortable. The average person would probably start to feel bothered at around eight pounds.

Or take a test where Im poked in the forearm with a needle. The device retracts into the handle like a Hollywood special-effects knife, so it doesnt pierce my skin, but it doesnt feel great I rate it a 7 out of 100. Then I get 10 pokes in quick succession. That hurts more, at 32. This is a normal response, but if I had central sensitization, I would likely have found the 10-poke series much more painful.

In addition to sorting out nociceptive or neuropathic from centralized pain, QST also seems able to reveal subtypes. In research published in 2017, three European consortia performed QST on 900 people with diverse pain conditions, all considered to be neuropathic. The testingseparated the subjects into three clusters, and the study authors predicted that each would be suited to different treatments.

Better-defined markers for different types of pain could radically improve pain management. As shown, it would allow patients to be sorted into clinical trials that would reveal the best treatments for each pain subtype. Results of those trials would help physicians treat individual patients more effectively.

The first cluster was characterized by deficits in sensation to touch, heat or pokes that would normally be painful. This suggests that central sensitization might be behind the pain in some of these people, says study coauthor Nadine Attal, a pain specialist at the Assistance Publique-Hpitaux de Paris. Opioids, antiepileptics or antidepressants (used for their effects on pain nerves, not mood) might help, because they act in the brain.

The second group was defined by extreme sensitivity to hot and cold like skin when its sunburned, which puts pain-sensing nerves on high alert. For this kind of neuropathic pain, local, numbing medications such as lidocaine, Botox or capsaicin (a therapeutic substance from hot peppers) might be the right choice.

People in the third group were particularly sensitive to pressure and pinpricks, and its members often reported pain akin to burning or electrical shock. This was a more complex group, Attal says; she thinks topical medications or antiepileptics might help. But now that researchers have the categories better defined, they can directly test medications to find what truly works best for each.

Looking at the brain in pain also can help scientists distinguish pain types, although the answers arent clear-cut. Theres no one, lone spot where pain lights up the brain, says Sean Mackey, chief of the division of pain medicine at Stanford University in California. Rather, the pain response is distributed across a circuit that encompasses several brain areas.

In the afternoon of my day as a pain-study subject, Im led to the universitys North Campus for an MRI. The technician slides me into a gray, General Electric-branded, upright donut about the size of a golf cart. The outside is festooned with frolicsome animal stickers (many subjects from other studies are children), but these do nothing to allay the discomfort of lying perfectly still with my head in a vise for an hour and a half.

As I lie there, listening to the scanners inharmonious beeps, rumbles and alien-laser-gun sounds, Im not thinking of anything in particular. Nonetheless, certain parts of my brain tend to draw blood at the same time, suggesting that theyre acting in sync. These are called networks.

Roughly half of people with rheumatoid arthritis experience pain even when using medications that control the inflammation. MRI scans of some of these patients reveal amped up connectivity between two brain regions, the default mode network and insula. This brain connectivity also has been found in people with fibromyalgia, a chronic pain condition with roots in the central nervous system. The discovery suggests that rather than inflammation alone, a dysfunctional central nervous system can also play a role in the pain of rheumatoid arthritis. (Credit: Image acquired and generated from the Chronic Pain and Fatigue Center with assistance from the FMRI laboratory at the University of Michigan)

One that Harris and colleagues are particularly interested in is called the default mode network. It turns on when Im at rest and my mind wanders to topics involving myself: what I had for breakfast, perhaps, or what Im planning for tonight once my day of pain is over.

Another network theyre watching is the salience network, which lights up when a person notices a new sensation say, the squeezing of their thumb to determine which sensations are worth responding to. It includes the insula, a pyramid-shaped bit of brain that Mackey and others have linked to pain.

Normally, the insula and the default mode network are unlikely to act at the same time. But Harris and colleagues discovered that in people with fibromyalgia,they were much more likely to flash in synchrony.

That makes sense, says Rob Edwards, a pain psychologist at Harvard Medical School and Brigham and Womens Hospital in Boston. For someone living with chronic pain, the pain can become a core part of their identity. The salience-related threat intrudes on, and even takes over, the way that you think about yourself, he says.

It may be possible to undo that intrusion, though. Edwards is currently testing cognitive behavioral therapy, or CBT, in people with fibromyalgia. In no way is he suggesting that their pain, or any pain, is imaginary, but therapy can help people deal with pain better and even reduce it. Its all about enforcing a sense of control and mastery, says Bob Kerns, a pain psychologist at Yale University in New Haven, Connecticut, who coauthored a paper in theAnnual Review of Clinical Psychologyonpsychological treatment for chronic pain.

In the study so far, CBT seems to be disentangling the salience and default mode networks in some people with fibromyalgia. Edwards predicts those people will also experience pain relief.

Being able to forecast who will benefit from a given treatment could make a huge difference not just for individual patients, but also in clinical trials for new pain-relief drugs. If scientists test a pain drug on 100 people, but only a fraction of those subjects actually have the pain mechanism the drug can treat, the medicine will look like a flop even if its a superstar for a particular subset of patients. This has almost certainly happened in past trials, Woolf says.

Mackey envisions a future in which pain patients can be tested for the underlying problem, perhaps with the same kinds of tests I underwent at the University of Michigan, plus many more assessments. For example, scientists are analyzing nerve endings in small skin samples from pain patients, and others aim to tease outthe role of genetics in chronic pain. Simple questionnaires can also help to identify pain types, all with this goal of prescribing medications tailored for a persons specific flavor of misery.

Medicine isnt quite there yet in fact, only 10 years ago Mackey would have called that scenario science fiction. Stay tuned, he says, because its no longer science fiction. . . . Were going to get there.

As required by the University of Michigan Institutional Review Board, Amber Dance was compensated $275 for her participation in the study at the Chronic Pain and Fatigue Research Center. She donated that amount tothe American Chronic Pain Association.

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

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There's More Than One Type of Pain. Scientists Are Learning to Treat Each of Them - Discover Magazine

Spinal Cord Stem Cells Comments Off on There’s More Than One Type of Pain. Scientists Are Learning to Treat Each of Them – Discover Magazine | January 22nd, 2020

Research team leader Marina Gomzikova, employee of the Gene and Cell Technologies Lab, started working on extracellular microvesicles (ECMVs) in 2013, when she was enrolled in her PhD course. Since then, very promising properties were found in ECMVs derived from human mesenchymal stem cells (MSCs).

ECMVs are microstructures surrounded by a cytoplasm membrane; they have proven to be a prospective therapeutic tool due to their biocompatibility, miniature size, safety, and regenerative properties. Microvesicles can be applied to circumvent the existing limitations in cell therapy without losing in effectiveness. At Kazan Federal University, cytochalasin B-induced membrane vesicles (CIMVs) are currently studied. They are derived from mesenchymal stem cells, which are very similar to natural ECMVs.

In this paper, the authors produced, studied and characterized the biological activity of MSC-derived CIMVs. A number of biologically active molecules were found in CIMVs, such as growth factors, cytokines, and chemokines; their immunophenotype was also described. Most importantly, CIMVs were found to stimulate angiogenesis, the growth of blood vessels, in the same way as stem cells.

Therefore, the team believes that human CIMVs-MSCs can be used for cell free therapy of degenerative diseases. CIMVs-MSCs are able to induce therapeutic angiogenesis, which is necessary for the treatment of ischemic tissue damage (for example, ischemic heart disease, hind limb ischemia, diabetic angiopathies, and trophic ulcers) and stimulate regeneration processes in cases of skin damage (wounds and burns), neurodegeneration (multiple sclerosis and Alzheimer's disease), or traumatic injuries (damage of peripheral nerves and spinal cord injury).

Gomzikova's group continues to research the therapeutic potential artificial microvesicles for autoimmune diseases. Vector properties, i. e. the capacity for delivery, of vesicles for tumor therapy is also of interest.

CIMVs can become a new therapeutic tool in regenerative medicine and a new class of effective and safe medications.

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Studies of membrane vesicles pave the way to innovative treatments of degenerative diseases - Science Codex

Spinal Cord Stem Cells Comments Off on Studies of membrane vesicles pave the way to innovative treatments of degenerative diseases – Science Codex | January 20th, 2020