TAMPA (FOX 13) - Repairing a damaged heart has become much more than opening clogged arteries in the Cardiac Catheterization Lab at Pepin Heart Hospital in Tampa.

Dr. Charles Lambert and his team are injecting stem cells directly into specific areas in the walls of damaged hearts.

"We know where viable tissue is, what part of the heart is contracting and has live cells there," he explains.

Finding that living tissue begins with creating a color-coded map of the heart identifying areas where blood flow is maximized.

"We go back after mapping with a needle that comes out of the catheter and we do roughly twenty injections in viable tissue area," Lambert says.

It's all part of an experimental clinical trial Shiela Allen hopes will help her failing heart recover. Less than two hours after welcoming her youngest grandchild into this world, her grandson drove her to the emergency room.

"I couldn't breathe," she recalled.

Sheila was shocked when doctors told her that her heart was pumping at less than half of what it should.

"Now that I look back, I can figure out I had all the symptoms but I was just putting it off because I'm busy, I'm old, I'm a little bit overweight," she admits.

Like many women, Sheila ignored warning signs like fatigue, coughing and shortness of breath - especially when lying down.

"The coughing was odd to me because I was not congested, I could not lay flat in bed so I was propped up on four or five pillows," she says.

Similar to a balloon filled with too much water, the cardiac muscle is overstretched, thin, and weak. So weak, it can only pump a fraction of the blood inside its chambers to the rest of the body. That causes fluid to back up into the lungs and other parts of the body like the legs.

For about a decade, cardiologists have tried using stem cells to strengthen the muscle with mixed results. This study is hoping a new twist, will make it more successful.

Along with using the heart map to direct the injections, the stem cells are also different. Instead of taking them from the patient, syringes like these are filled with stem cells from donors.

"These trial cells are taken from healthy volunteers that are actually medical students, not here in town, but actually up in the northeast," he explains.

Another key difference in the study is the product's maker, Mesoblast. It is allowing people like Sheila, who have heart failure from unknown causes, to also enter the study. The clinical trial using the younger cells is now in 50 centers across the world.

"They're preserved so when we randomize a patient we take it off the shelf, treat it, warm it, the cells are perfectly alive and healthy and then administer it to the patients," Lambert says.

Side effects in earlier studies included a drop in blood pressure, bleeding, and fluid accumulation around the heart.

"It was basically like I was having another heart catheterization," Sheila says her side effects were minimal. "Three days after the procedure I was on a plane going on a trip."

She's not sure if she got a placebo or the actual cells, but as she completes her cardiac rehabilitation therapy, she says she is feeling better, "I've had a little more energy I dont know if it's related to that."

Energy allowing her to spend time with her family, and watch her youngest grandchild grow.

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Damaged hearts being repaired with stem cells - FOX 13 News, Tampa Bay

From left to right: Richard Stone, a doctor at Dana-Farber Cancer Institute in Boston, poses with Peter Karalekas (center), 76, and Matthew Churitch, 22. Churitch donated stem cells to Karalekas two years ago, and he visited Dana-Farber with Karalekas earlier this summer. (Courtesy photo)

BOSTON -- After winding his way through Massachusetts, Connecticut, New Hampshire and Maine for 76 years, Peter Karalekas has a proclamation: He's a Southerner now.

He still lives in Kittery, Maine, just about an hour from the Lowell middle school where he taught for 21 years.

He has no plans to move.

Rather, Karalekas considers himself a Southerner because of his stem cells.

He never exactly felt all that sick.

Karalekas worked tirelessly for decades, first as a teacher and coach at the James S. Daley Middle School in Lowell and then as the owner of a half-dozen T-Bones restaurants across New Hampshire.

Even despite the 12-hour days, seven days a week, in the grind of the restaurant industry, Karalekas felt healthy and rarely fell ill.

Peter Karalekas, left, a 76-year-old former Lowellian, smiles during his first meeting with Matthew Churitch, 22, of Nashville, Tennessee, who helped save Karalekas life by donating stem cells. (Courtesy photo)

The two, who do not have children, moved to Kittery 17 years ago.

Everything started to change in 2014.

Karalekas recalls being "short-winded," but he had very few other symptoms when he was diagnosed with myelodysplastic syndrome, a rare type of cancer in which the bone marrow is damaged and cannot produce enough blood cells.

The prognosis was not good.

"They said the only thing that would save me was a stem cell transplant," Karalekas said. "Otherwise, I had a couple of months to live, because my cells were all dropping drastically.

He went onto a registry, hoping for a donor to pop up, but doctors told him it could take from six months to two years to find the right match. Even with a transplant, Karalekas said, his chances of success were "30 to 40 percent."

The call came four weeks later.

Matthew Churitch got his call quickly, too.

He joined the National Marrow Donor Program's Be the Match Registry in 2014, the summer between his freshman and sophomore years at Clemson University. His mother had been on the registry to donate for years. Churitch's decision was simple: When a friend was diagnosed with leukemia, he knew he should sign up, too.

He did the requisite cheek swab, unsure if he would ever even be contacted to donate. By the time he had finished the following semester, he got the call.

A match was found.

Churitch went through several more levels of testing and preparation to donate stem cells to a stranger. He went to Clemson's student health center to have blood drawn.

He returned to his native Nashville, Tennessee, going to a medical center 10 days in a row to receive shots in his stomach that would stimulate his bone marrow and prepare his cells for transplant.

He sat for eight hours, a needle in each arm as his stem cells were filtered out so they could be transferred to Boston.

"Getting the shots isn't fun," he said. "You're pretty sore afterward for a few weeks. But knowing that the person on the other end is in hundreds and hundreds times more pain than any donor would ever go through -- that kind of pushed me through."

Karalekas and Churitch first connected via an anonymous letter, per the transplant registry's rules, updating Churitch on Karalekas's lengthy, isolated recovery. They were able to speak directly after a year.

Churitch dialed Karalekas' number on a lengthy walk to class, took a deep breath and hit the call button. Moments later, both men were crying and laughing.

"That was really awesome, just being able to hear his voice and recognize that there's somebody else on the other end of this," Churitch said. "A lot of people don't get the chance to connect with their recipients or their donors."

Karalekas wanted more. He told his wife early on that he wanted to meet his "angel from heaven," so when Churitch graduated Clemson earlier this year, Karalekas paid to bring the 22-year-old and his mother to New England.

In late June, Karalekas and his wife pulled into a pickup lane at Logan International Airport in Boston.

"I got out of the car, I charged over, and I gave them both a huge hug," Karalekas said.

Karalekas showed Churitch and his mother around for five days.They went on a private tour of Fenway Park; they wandered the historic streets of Portsmouth, New Hampshire; they visited Dana-Farber together to meet the team that treated Karalekas.

Both families quickly bonded. Karalekas recalls his brother George asking Churitch about his portable phone charger, expressing curiosity about how convenient it was. A few weeks later, a brand-new portable charger arrived at George's door, a gift from Churitch.

In January, Karalekas and his wife will vacation in Arizona and will cheer on Churitch's mother -- without Churitch even present -- in the Phoenix Marathon.

Donor and recipient talk every week.

"It's like we're a very, very close-knit family now," Karalekas said. "He's the son we never had."

Churitch is now in his first year at the University of South Carolina School of Medicine Greenville with hopes of becoming a physician. He hopes to use Karalekas's experience as inspiration for any patients facing future hardship, and he hopes that others, especially young people, will see their success and join the registry.

"You never know where that will take you," he said. "You can gain a friend for life, impact somebody and their family in need."

Karalekas said he feels he has a new life: His chances of beating the disease are now 97 percent, he says, up from the 30 percent or 40 percent when he started treatment. Thanks to the transplant from a handsome, athletic college student in Tennessee.

"I said, 'I'm a Southerner now,'" Karalekas said. "My stem cells are 99 percent this gentleman. I'm 99 percent him."

Follow Chris on Twitter @ChrisLisinski.

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For Lowell native, stem cell match becomes a match as friends - Lowell Sun

A team of scientists found a way to create a novel drug delivery system for an array of different conditions.

Researchers at the Fred Hutchinson Cancer Research Center developed a biomedical tool that harnesses nanoparticles to deliver transient gene changes to specified cells.

This system extends the therapeutic potential of messenger RNA (mRNA). This biological element is responsible for delivering molecular instructions from DNA to other cells in the body making them produce proteins to prevent or attack a disease.

The technique involves mixing freeze-dried nanoparticles with water and a sample of cells.

"Our goal is to streamline the manufacture of cell-based therapies," said lead author and biomaterials expert Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division, in a statement. "In this study, we created a product where you just add it to cultured cells and that's it -- no additional manufacturing steps."

Heres how this technology worked in three experiments targeting T-cells in the immune system and blood stem cells in a process they called hit-and-run genetic programming.

The team imbued these nanoparticles with a gene editing tool and sent them to T-cells residing in the immune system to snip out their natural T-cell receptors. They were then paired with genes encoding a CAR, otherwise known as a chimeric antigen receptor, designed to attack cancer.

Next, the researchers engineered the nanoparticles to target blood stem cells. They were equipped with mRNA that enabled the stem cells to multiply and replace blood cancer cells with healthy cells when used in bone marrow transplants.

Finally, the nanoparticles were targeted to CAR-T cells containing foxo1 mRNA that signaled to the anti-cancer T-cells to develop into a form of memory cell that exhibits more aggressive behavior and destroys tumor cells more effectively.

Other attempts to engineer the mRNA into disease-fighting cells were more difficult. The large messenger molecules degraded quickly before it could make it have an effect while the bodys immune system recognized it as foreign.

Still, this process could replace the more labor-intensive alternative called electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms.

Stephan is currently looking for commercial partners to help move into clinical trials.

The study was published in the journal Nature Communications.

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Nanoparticle Advance Could Yield Multi-Purpose Treatments - Drug Discovery & Development

Parkinsons stem cell breakthrough

Miodrag Stojkovic/Science Photo Library

By Helen Thomson

MONKEYS with a Parkinsons-like disease have been successfully treated with stem cells that improved their movement for up to two years after transplant. A similar trial is now being prepared for people.

Parkinsons destroys dopamine-producing cells in the brain, leading to tremors and difficulty moving. Previous experiments using stem cells from embryos have shown promise in replacing lost cells, but the use of these is controversial.

Jun Takahashi at Kyoto University, Japan, and colleagues wondered whether they could treat monkeys with a disease like Parkinsons using induced pluripotent stem cells, which are made by coaxing blood or skin cells into becoming stem cells.

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The team generated stem cells from three people with Parkinsons and four without the disease. They then transformed these into dopamine-producing brain cells.

All the monkeys who received injections of these cells showed a 40 to 55 per cent improvement in their movements, matching results from previous experiments with embryonic stem cells. Monkeys who had a control injection minus the cells didnt improve (Nature, DOI: 10.1038/nature23664).

Stem cells from people with and without Parkinsons were equally effective. The monkeys became more active and showed less tremor, says Takahashi. Their movements became smoother.

After the transplant, the monkeys were given immunosuppressive drugs to prevent the new cells from being rejected and observed for up to two years. No serious side effects appeared during this time.

This study shows that the stem cells behave as you would like them to and they appear safe, says Roger Barker of the University of Cambridge. All of which gives one greater confidence in moving to human studies.

This article appeared in print under the headline Parkinsons stem cell breakthrough

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Human blood and skin cells used to treat Parkinson's in monkeys - New Scientist

A brain cell replacement therapy reduced Parkinsons disease symptoms in monkeys, Japanese researchers report in a study released Wednesday. The positive result boosts prospects to test the therapy in people.

The goal is to implant neurons derived from stem cells into the brains of Parkinsons patients, a project pursued by scientists in San Diego, New York, Britain and Sweden as well as in Japan. If all goes well, the neurons will function as replacements for those destroyed in the disease.

In addition, human testing of a related brain cell therapy from Carlsbads International Stem Cell Corp. is already under way in Australia.

While treatments exist for the movement disorders caused by Parkinsons, none of them actually halt progression. Replacing the brain cells destroyed in Parkinsons holds the promise of actually reversing the disease.

Moreover, success with Parkinsons could pave the way to treating many other neurodegenerative diseases, such as ALS (Lou Gehrigs disease) and perhaps Alzheimers, along with brain and spinal cord injuries. These afflictions cost hundreds of billions annually, and most importantly, produce immense suffering in patients and caregivers.

Years of extensive research are required before any such therapy can be tried in people. Testing in monkeys or other primates is often regarded as the last step before human treatment can be contemplated.

The study was published in the journal Nature. Its senior author was Jun Takahashi, a prominent stem cell researcher at Kyoto University in Kyoto, Japan. Go online to j.mp/parkips for the study.

There is precedent to suggest the therapy might work. Beginning decades ago, brain cells taken from human fetuses have been implanted into the brains of Parkinsons patients, with mixed results. Some patients experienced improved movement control. But others gained nothing, or experienced uncontrolled movements.

Scientists in the field say using stem cells should provide improved results. Stem cells can be made in greater quantity than the limited number of fetal brain cells available. In addition, the stem cells and neurons made from them can be analyzed for quality before implantation.

The study was praised by regenerative medicine researcher Tilo Kunath at the University of Edinburgh, in comments provided by the UK Science Media Centre.

This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinsons can be produced in the lab, Kunath said.

Such a therapy has the potential to reverse the symptoms of Parkinsons in patients by restoring their dopamine-producing neurons. The next stage will be to test these therapies in a first-in-human clinical trial.

In the study, researchers produced neurons that secrete dopamine, a neurotransmitter deficient in Parkinsons disease. These neurons were made from human stem cells derived from both healthy people and those with Parkinsons.

The researchers then implanted the human neurons into 10 monkeys whose own dopamine-making neurons had been destroyed. The monkeys were given immunosuppressive drugs to prevent rejection of the human cells.

The human neurons integrated into the brains of the monkeys and functioned as dopamine-making neurons. The monkeys improved in movement ability, save for one monkey that became ill and was euthanized. Both cells from healthy and Parkinsons patients were effective.

A companion study in Nature Communications demonstrated a method of immune-matching the cells to reduce the immune response. Takahashi was also senior author of that study. Go online to j.mp/ipsimmune for the study.

Both studies used artificial embryonic stem cells, called induced pluripotent stem cells (IPS). These act-alike cells are not derived from embryos, but are genetically reprogrammed from adult cells, usually skin cells.

The IPS cells appear to act virtually identically to embryonic stem cells, but dont raise the ethical objections many have to using embryonic stem cells. These cells were invented in 2006 by a team led by Shinya Yamanaka, a co-author of the Nature Communications study.

Moreover, the cells can be made from the patients themselves, which is not expected to cause an immune reaction. This is the approach taken by the San Diego team, including scientists at The Scripps Research Institute.

Carlsbads International Stem Cell Corp. uses a different approach. It starts with unfertilized, or parthenogenetic, human egg cells. These are grown into immature neurons that are implanted. The cells are expected to grow not only into dopamine-making neurons, but other kind of brain cells that preserve the remaining neurons.

The Australian clinical trial has gathered evidence of safety, and continued testing is under way determine efficacy.

The Nature study dovetails with research by the San Diego group, Summit for Stem Cell, (www.summitforstemcell.org), including scientists at The Scripps Research Institute and doctors at Scripps Health.

The group proposes to treat Parkinsons patients with neurons grown from their own IPS cells. The scientists have received funding from the California Institute for Regenerative Medicine, the states stem cell agency.

The studies support the personalized approach that we are taking for a neuron replacement therapy for Parkinson's disease patients, said Jeanne Loring and Andres Bratt-Leal, stem cell scientists at The Scripps Research Institute.

Two points from the studies should be highlighted, Loring and Bratt-Leal said by email.

Parkinson's disease is a late-onset disorder, they said. That means that there was nothing wrong with the neurons that people with Parkinson's were born with. Few PD patients have a family history of the disease, which suggests that genetic mutations did not cause their disease.

So for the great majority of patients, transplantation of their own neurons is a promising approach to relieving symptoms, without having to take expensive and risky immunosuppressive drugs, they said.

The Summit for Stem Cell scientists are members of an international partnership of laboratories developing neuron replacement therapies for Parkinsons, called GForce PD.

Takahashi belongs to the partnership, as do scientists in the UK, Sweden and New York. These use both embryonic and IPS stem cells. The Summit for Stem Cell effort is the only one using patient-matched IPS cells, Loring and Bratt-Leal said.

Brain cells reprogrammed to make dopamine, with goal of Parkinsons therapy

Parkinson's stem cell therapy shows signs of safety

Parkinson's therapy funded by California's stem cell agency

Dopamine-making neurons can be chemically controlled in animal model of Parkinson's

Stem cell clinical trial for Parkinson's begins

Summit for Stem Cell

bradley.fikes@sduniontribune.com

(619) 293-1020

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Brain cell replacement for Parkinson's boosted by monkey study - The San Diego Union-Tribune

A diagram of a scaffold loaded with CAR T cells and microspheres containing nutrients to help the cells multiply and then leave the scaffold to go attack cancer cells. Credit: Cognition Studio, courtesy of Fred Hutchinson Cancer Research Center.

A new biomedical tool using nanoparticles that deliver transient gene changes to targeted cells could make therapies for a variety of diseasesincluding cancer, diabetes and HIVfaster and cheaper to develop, and more customizable.

The tool, developed by researchers at Fred Hutchinson Cancer Research Center and tested in preclinical models, is described in a paper published August 30 in Nature Communications.

"Our goal is to streamline the manufacture of cell-based therapies," said lead author Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division and an expert in developing biomaterials. "In this study, we created a product where you just add it to cultured cells and that's itno additional manufacturing steps."

Stephan and his colleagues developed a nanoparticle delivery system to extend the therapeutic potential of messenger RNA, which delivers molecular instructions from DNA to cells in the body, directing them to make proteins to prevent or fight disease.

The researchers' approach was designed to zero in on specific cell typesT cells of the immune system and blood stem cellsand deliver mRNA directly to the cells, triggering short-term gene expression. It's called "hit-and-run" genetic programming because the transient effect of mRNA does not change the DNA, but it is enough to make a permanent impact on the cells' therapeutic potential.

Stephan and colleagues used three examples to demonstrate their technology:

Other attempts to engineer mRNA into disease-fighting cells have been tricky. The large messenger molecule degrades quickly before it can have an effect, and the body's immune system recognizes it as foreignnot coming from DNA in the nucleus of the celland destroys it.

Stephan and his Fred Hutch collaborators devised a workaround to those hurdles.

"We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation," Stephan said. The researchers surrounded the nanoparticle with a negatively charged envelope with a targeting ligand attached to the surface so that the particle selectively homes in and binds to a particular cell type.

The cells swallow up the tiny carrier, which can be loaded with different types of manmade mRNA. "If you know from the scientific literature that a signaling pathway works in synergy, you could co-deliver mRNA in a single nanoparticle," Stephan said. "Every cell that takes up the nanoparticle can express both."

The approach involves mixing the freeze-dried nanoparticles with water and a sample of cells. Within four hours, cells start showing signs that the editing has taken effect. Boosters can be given if needed. Made from a dissolving biomaterial, the nanoparticles are removed from the body like other cell waste.

"Just add water to our freeze-dried product," Stephan said. Since it's built on existing technologies and doesn't require knowledge of nanotechnology, he intends for it to be an off-the-shelf way for cell-therapy engineers to develop new approaches to treating a variety of diseases.

The approach could replace labor-intensive electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. All the handling ends up destroying many of the cells, which limits the amount that can be used in treatments for patients.

Gentler to cells, the nanoparticle system developed by the Fred Hutch team showed that up to 60 times more cells survive the process compared with electroporation. This is a critical feature for ensuring enough cells are viable when transferred to patients.

"You can imagine taking the nanoparticles, injecting them into a patient and then you don't have to culture cells at all anymore," he said.

Stephan has tested the technology is cultured cells in the lab, and it's not yet available as a treatment. Stephan is looking for commercial partners to move the technology toward additional applications and into clinical trials where it could be developed into a therapy.

Explore further: Implanted scaffold with T cells rapidly shrinks tumors

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Nanoparticles loaded with mRNA give disease-fighting properties to cells - Medical Xpress

A new review looks at the potential of fetal membranes, which make up the amniotic sac surrounding the fetus during pregnancy, for regenerative medicine.

Fetal membranes have been used as biological bandages for skin grafts as well as for serious burns. They may also have numerous other applications because they contain a variety of stem cells, which might be used to treat cardiovascular and neurological diseases, diabetes, and other medical conditions.

"The fetal membranes have been used successfully in medical applications for over a century, but we continue to discover new properties of these membranes," said Dr. Rebecca Lim, author of the STEM CELLS Translational Medicine review. "The stem cell populations arising from the fetal membranes are plentiful and diverse, while the membrane itself serves as a unique biocompatible scaffold for bioengineering applications."

Explore further: Stem cell research could prevent premature births

More information: Rebecca Lim. Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?, STEM CELLS Translational Medicine (2017). DOI: 10.1002/sctm.16-0447

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Fetal membranes may help transform regenerative medicine - Medical Xpress

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KING OF PRUSSIA, Pa., Aug. 28, 2017 /PRNewswire/ --Global biotherapeutics leader CSL Behring announced today that it has agreed to acquire Calimmune, Inc., a biotechnology company focused on the development of ex vivo hematopoietic stem cell (HSC) gene therapy with R&D facilities in Pasadena, California and Sydney, Australia for an upfront payment of $91 million.

The acquisition will provide CSL Behring with Calimmune's pre-clinical asset, CAL-H, an HSC gene therapy for the treatment of sickle cell disease and -thalassemia, which complements CSL Behring's current product portfolio and deep expertise in hematology.

Additionally, CSL Behring will acquire two unique proprietary platform technologies, Select+ and Cytegrity. These technologies are designed to address some of the major challenges currently associated with the commercialization of stem cell therapy, including the ability to manufacture consistent, high-quality products, and to improve engraftment, efficacy and tolerability. Both technologies have broad applications in ex vivo stem cell gene therapy.

"Calimmune shares in our promise and focus to improve the lives of patients with rare and serious medical conditions," said CSL Limited Chief Executive Officer and Managing Director, Paul Perreault. "The acquisition represents another important step in the execution of our strategy for sustainable growth."

"Calimmune's scientific accomplishments are impressive," Perreault added. "The team has built a robust technology platform, and designed a promising HSC gene therapy candidate - CAL-H, which strongly aligns with our longer-term strategic goals, and complements our core competencies and areas of therapeutic focus. While Calimmune is still in the early stages, we believe that our combined strengths have tremendous potential to change treatment paradigms, and most importantly, significantly improve the lives of our patients."

Calimmune Chief Executive Officer Louis Breton said, "We are excited to become part of CSL Behring. They are an established global industry leader in protein-replacement therapies and have a proven track record of driving innovations through the development pipeline and delivering differentiated products to the global marketplace. Together, we are well positioned to take our achievements to the next level."

CAL-H, Calimmune's HSC gene therapy for sickle cell and -thalassemia, employs both the Select+ system, and the Cytegrity virus production platform. CAL-H has yielded early positive preclinical results and demonstrates the potential to offer a significant advantage to patients suffering from these currently incurable genetic diseases.

Both proprietary technologies have the potential to be used in treatments for a wide range of other rare diseases that would complement CSL Behring's business, including those within the company's current product portfolio.

About Sickle Cell Disease and thalassemiaSickle cell disease and -thalassemia are inherited disorders that affect hemoglobin, the protein in red blood cells that carries oxygen to different parts of the body. They are chronic diseases that dramatically impair the function of many organs and are associated with substantial morbidity, poor quality of life and a shortened life expectancy. The severe forms of both these diseases remain areas of high unmet need with sickle cell disease affecting approximately 150,000 Americans and Europeans and -thalassemia approximately 16,000. Although there are effective treatments available to relieve the symptoms of these diseases, there are no disease modifying treatments and in many cases regular blood transfusions are also required. Bone marrow transplant has been shown to be an effective cure in children, however, is rarely done due to the lack of closely matched donors.

About Select+ Calimmune's Select+TM is a proprietary technology aimed at driving selection of the genetically modified stem cells once they are given back to patients, to decrease toxicity and improve efficacy. One of the historical challenges for gene therapy is achieving a high enough engraftment of stem cells in the bone marrow to reach the relevant therapeutic window. Toxic conditioning regimens used to drive engraftment of gene modified cells can cause a range of adverse events that often require hospitalization and have additional long-term risks.Calimmune has focused on and made significant investments in solving this issue with Select+TM.The combination of Select+TM and lentiviral therapeutic applications aims to reduce the conditioning regimens, increase engraftment and overall efficacy, and improve the patient experience, ultimately making stem cell gene therapy an out-patient modality.

About Cytegrity Calimmune's CytegrityTM is a scalable manufacturing technology for the production of lentiviral vectors, which are used as a delivery mechanism for gene therapy. Lentiviral vectors are traditionally manufactured in small batches through a convoluted process; Cytegrity represents a new system that increases consistency and quality, and significantly lowers costs.

Transaction & Closing CSL Behring will have operational control ofCalimmune following closing of the transaction. In addition to the upfront payment, theagreement between the parties includes the potential for performance based milestone payments of up to $325 million over a period currently anticipated to be around eight years or more following the closing of the transaction.The transaction is expected to close within the next two weeks, subject to the satisfaction of various closing conditions.

Weil, Gotshal & Manges LLP acted as legal advisor to CSL Behring. Piper Jaffray & Co. acted as exclusive financial advisor and Cooley LLP acted as legal advisor to Calimmune.

About Calimmune Calimmune is a privately owned company committed to accelerating the promise of gene therapy to liberate patients from chronic and currently incurable diseases. To achieve this ambitious goal, Calimmune has built a suite of technologies to advance the delivery, manufacturing, and overall efficiency of these life-changing medicines. Calimmune's lead development programs are novel ex vivo gene therapies for hematologic diseases.

About CSL BehringCSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients' needs by using the latest technologies, we develop and deliver innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, inherited respiratory disease, and neurological disorders. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic disease of the newborn.

CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. The parent company,CSL Limited(ASX:CSL; USOTC:CSLLY), headquartered in Melbourne, Australia, employs nearly 20,000 people, and delivers its life-saving therapies to people in more than 60 countries. For more information visitwww.cslbehring.comand follow us on http://www.Twitter.com/CSLBehring.

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CSL Behring to Acquire Biotech Company Calimmune and its Proprietary Stem Cell Gene Therapy Platform - Markets Insider

NICEVILLE, Fla. (AP) Jack Massey is ready to go back to school.

Only this time, the University of Florida senior will head back to campus with his mom and a new outlook on life.

Massey suffered a spinal cord injury in a pool accident in March and is paralyzed from the chest down. After months of rehab, he's eager to get back into a familiar routine.

"It's definitely boring," the 21-year-old said at his parents' home in Niceville. "There's not a lot to do. I want to go back to school. I still have my brain. I still have everything I need to be successful."

After the accident March 17, Massey was treated at the University of Florida Shands Hospital and then was transferred to Shepherd Center, a spinal cord and brain injury rehab center in Atlanta. At Shepherd Center he met with a peer mentor, counselors and physical therapists to help him find a new normal.

Jack has remained positive throughout the past six months.

"Jack has been a fighter through all of this," said his mother, Julie. "I think he's done well. I only saw him break down once."

Before the accident, Jack was a well-rounded athlete who playing baseball and basketball and ran. He was a star on the track and field team at Niceville High School, with his 4 X 800 relay winning state his senior year.

He says the biggest challenge now is not being able to do the same things he could before.

"I can't get up and go," he said. "It didn't really start to set in until after I got out of rehab."

Jack has had to find enjoyment in other things, like reading or playing with the dogs. His friends have learned to transfer him from his wheelchair to a car so they can take him to the movies or out to eat. When they recently took a trip to the beach, Julie said five of Jack's friends carried him out to the sand a lesson on how hard it is to navigate the world in a wheelchair.

Jack said he believes technology one day will advance enough that he won't be paralyzed forever. He also volunteered to do stem cell surgery to allow doctors to study the effects of stem cells on his spine for the next 15 years. Instead of wallowing in self-pity, he's moving forward. But he'll need help.

"I'm appreciating everything in the now," he said.

Doctors have said Jack has adapted faster than expected, but there are still some everyday essential tasks that are out of his reach. He cannot write or cook. He can shower himself but can't dry himself or transfer himself in and out of his wheelchair. The Massey family hopes to secure a personal care attendant for Jack at school, but until then Julie will be in Gainesville to help him transition. An occupational therapy student from the university will also help Jack on a temporary basis.

Finding proper care for her son has proven to be a learning experience for Julie and her husband, Lance.

"I don't know how people do it," she said. "We have good health care, but then there's hidden costs. There's travel expenses. ... It's kind of humbling. Nobody should have to go to GoFundMe for medical help."

Jack wants to spend his final year as an undergrad as independent as possible. After months of helping him recover, Julie said it will be hard to let her son go. Jack is the oldest of three; his brother Lance is 19 and a student at UF and his sister Alina is 14 and attends Ruckel Middle School.

"It's like letting him go off to kindergarten again," she said.

As for life after college, Jack said he doesn't feel limited in career choices. One of his professors in the geology department encouraged him by saying that there were plenty of opportunities he could pursue in that field. Jack said he may also consider law school. One thing he's learned through this life-altering experience is that there are no limits to what he can achieve.

"I haven't done that much deep thinking. I just go with the flow," he said. "But I learned I have more perseverance. I'm more mentally tough than I thought I was. I'm appreciative for life in general. That's one of the big things."

___

Information from: Daytona Beach (Fla.) News-Journal, http://www.news-journalonline.com

See the rest here:
Paralyzed after pool accident, student heads back to college - San Francisco Chronicle

It will take you just a few hours to donate stems cells but it will save someones life as it is usually the last or the only resort for those suffering from blood cancer. Stem cells are undifferentiated biological cells that can grow into specialized cells. There are two types of stems cells, which are embryonic stem cells and adult stem cells. Embryonic stem cells are extracted from theblastocyst, which is a structure that contains cell mass that develops into an embryo. Adult stem cells are the undifferentiated cells that replenish the dying cells or repair the damaged cells. These adult stems cells are donated during the stem cell donation. Stems cells are transferred to the patient, where it differentiates into healthy specialized cells. (ALSO READMajor blood types and who can donate blood to whom).

Stem cell donation is voluntarily donating the stem cells produced by your body. It can be donated in two ways. The first method is called Peripheral blood stem cell (PBSC) donation while the other method is bone marrow donation. Bone marrow donation requires hospitalization. Bone marrow is collected from your pelvis by doctors under general anesthesia using a syringe. You may experience pain and bruise but you will recover within a week.

Peripheral blood stem cell donation is used by 90 percent of the people to donate stem cells. It is an easy and quick process to collect the blood-forming cells found in the circulating blood. This non-surgical process of collecting the stem cells is called apheresis.

You need to register to donate stem cell. Your cell sample from cheek is analyzed for HLA typing and when there is a requirement for stem cell with your HLA type, you will get a notification. A complete health check-up is carried out to ascertain that you are fit to donate the stems cells. Once the check up is done, you will be given an injection called GCSF (Granulocyte Colony Stimulating Factor)to increase the stem cell present in your blood. This injection will be administered for five days and on the fifth day, the stem cells are collected. A tiny tube will be inserted in your arm and this tube is connected to a machine that will collect the stem cells. Your blood will pass through the machine. This procedure usually takes about five hours. You may experience flu like symptoms after donating the stem cells but it will soon subside.

Your cells will be given to those suffering from blood cancer and it could save the life of that person.

View original post here:
What is stem cell donation: How does peripheral blood stem cell collection work? - India.com

There are many claims that stem cells possess anti-ageing properties and other secrets to youth and regeneration. However, there has not been much scientific proof demonstrating these touted abilities.

Dr Paul Lucas, an assistant professor of orthopaedics and pathology from the New York Medical College in the United States, notes that the words stem cells are thrown around far too casually, and that many people assume that they are a single type of cell.

The definition of stem cell is an operational definition.

That is, it describes what the cell can do, and not any particular protein or other marker it can make, he says.

According to him, a stem cell is a cell that can:

Differentiate into at least one phenotype (cell type), and

Has the ability to divide, with at least one daughter cell remaining a stem cell.

Lots of hype, very little biology. I have written several answers on the website Quora that address this.

Pills and creams are not legit.

The skin has a barrier called the stratum corneum that prevents bacteria from getting inside the body.

The stratum corneum will also block stem cells, which are much, much larger than bacteria, in the form of a cream.

Any stem cell will not survive in a pill with no water. And of course, any cell will not survive the hydrochloric acid in the stomach.

So there is no way stem cells in either a pill or a cream can get inside the body.

Even if a stem cell could get inside the body, there is very little data that any stem cell will be anti-ageing its a way to separate people from their money.

There are several reasons stem cells do not counter ageing.

Stem cells are not magic. They are not magic pixie dust you can sprinkle on everything and make it be perfect.

Ageing has many causes. One of them is DNA and cellular damage.

It is thought that the various adult stem cells are the cells of origin of cancer. The data is very solid for at least hepatomas and leukaemias.

That means that stem cells can suffer mutations that alter cellular function degrading it in some cases, and causing it to go haywire and be cancer in others.

Also, how are stem cells to be injected? Into each tissue? Every muscle, organ, tendon, ligament, etc?

Or are the stem cells to be injected into a vein and travel to all parts of the body?

There are two technical problems with this:

Injecting into a vein means that most of the cells are going to be trapped in the lungs before they go out to the rest of the body, as our veins all lead first to our heart, then our lungs.

Blood vessels are sealed tubes. Think pipes.

Just how are the stem cells supposed to exit the pipes?

This is especially true for reversing ageing in the most important organ the brain.

The neural tissue in the brain is separated from the blood vessels by another layer of tissue called the blood-brain barrier.

Even if stem cells got out of the blood vessels in the brain, they are not going to get to the neural tissue, which is the tissue that needs to rejuvenate.

There is no way any injected stem cells are just going to magically replace all the aged cells in the body.

Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Photo: 123rf.com

Plants are very different from us. No cell from a plant is going to be able to incorporate into our tissues and act like a stem cell.

Many mammalian stem cells particularly mesenchymal stem cells synthesise and secrete several proteins.

Some of these proteins are growth factors in that they cause other cells to divide.

The claim seems to be that plant growth factors will have the same effect on human cells as they do on plant cells.

That is false.

Even some of the skincare people admit this. The following quote is from the website of a US-based skincare company that uses both human and plant stem cells: That said, unlike human stem cells, the growth factors, cytokines and other proteins, which are the products of plant stem cells, do not have the ability to act in the same way in humans, as in plants.

Plant stem cells communicate in a different biochemical language that human cells do not recognise.

First is the source.

ESCs are the inner cell mass of a five to seven-day-old blastocyst, which is formed after the sperm successfully fertilises the egg.

PSCs come either from the tissue of the placenta itself or from the Whartons jelly of the umbilical cord.

Secondly, ESCs are pluripotent, meaning they are able to differentiate into every tissue of the body. They can also form tumours in our body.

PSCs are essentially adult stem cells that have limited proliferation potential, i.e. the cell has a fixed number of times it can divide before it dies. They are multipotent, meaning that they have the ability to form more than one cell type, and do not form tumours.

Probably less costly, but no more effective.

The treatment uses mesenchymal stem cells (MSCs).

The discoverer of MSCs Prof Dr Arnold Caplan says they should be called mesenchymal secreting cells. Notice that he does not consider them stem cells!

MSCs secrete a large number of cytokines that reduce inflammation. It is inflammation that causes pain.

Aspirin, ibuprofen, and naproxen also reduce inflammation.

A stem cell injection with MSCs is essentially putting little aspirin factories at the site of injury.

They reduce the pain, but do little or nothing to regenerate the tissue.

For young athletes, reducing inflammation will allow the bodys healing process to work better, and thus, improve outcome.

For older patients? There is less capacity for healing.

Read more:
Are stem cells really the fountain of youth? - Star2.com

Hope is surely on the way for children with special needs as Alok Sharma, a world renowned neurosurgeon, Neuroscientist and professor, a director of NeuroGen Brain and Spine Institute India visited Nigeria recently to shed light on the efficacy of stem cells in treating children with special needs.With over 5000 patients treated from 50 countries, 68 scientific papers and 14 published books, and an overall 91% success rate, Alok was determined to enlighten participants who attended the one day seminar on stem cell awareness and its importance.According to Asok, We are the pioneers of introduction to Stem Cell Therapy for neurological disorders. We make use of holistic, comprehensive approach to treat our patients with a combination of stem cell therapy and neuro-rehabilitation. We use adult stem cells derived from the patients own bone marrow, as they are the safest and most feasible type of cells. Since every patient is different, our treatment protocol is customised according to the patients requirements.We now have a treatment that is very effective and a large number of people can benefit from this. The old thinking was that when the central nervous system is damaged then it is beyond repairs but the new thinking is that some degree of repair is possible. Stem cells have three capabilities. They repair, regenerate or replaced. It took us between seven to eight years to prove that stem cells can convert to nerve cells and when we became very sure, we went on to use on humans and the results have been outstanding He said.Asked who can be treated with the stem cell procedure and Asok says for paediatric, we treat children with autism, cerebral palsy, intellectual disability and muscular dystrophy. For adults, we treat spinal cord injury, stroke, traumatic brain injury/head injury, motor neuro disease/amyotrophic lateral scierosis and other neurological disorders.Asok explains that there are many types of stem cells used, but broadly they can be classified into 3 types:-Embryonic stem cells: Embryonic stem cells, as their name suggests, are derived from 3-4 day embryos. These are obtained from spare embryos from IVF clinics with the consent of the donor. During this early developmental period, the cells that will ultimately give rise to the developing fetus can be encouraged to develop into tissues of different origins (totipotency) contributing greatly to stem cell therapy. However, there are many ethical and medical issues regarding its use. These are therefore, not being used presently.Umbilical cord stem cells: These cells are derived from the umbilical cord which connects the baby and the mother at birth. Stem cells derived from the umbilical cord are stored by various cord blood banking companies. These stem cells do not have any major ethical issues surrounding their usage, but availability can be a problem.Adult stem cells: They can be derived from the same patient, from either the hip bone or the adipose/fat tissue. Currently, they are the most popularly used stem cells. The benefits that adult stem cells offer are:1, They are available in abundance and can be isolated easily.2, They are isolated from patients, which overcomes the problem of immunological rejection.3, Adult stem cells have the potential to replenish many specialized cells from just a few unspecialized ones.4, They do not have any ethical issues as they do not involve destruction of embryos.5, The risk of tumor formation is greatly reduced as compared to the use of embryonic stem cells.There are fears about stem cell therapy but Asok cleared the air when he said this isnt the truth as the one feared is the embryonic stem cells (ESCs) which are stem cells derived from the undifferentiated inner mass cells of a human embryo. ESCs are just one of the types of stem cells but we do not make use of that in our hospital as explained earlier, we use Adult Stem Cells. We do not use the embryotic stem cells because they have the tendency to become tumours in the body. He explained.On how the procedure works, he says a thin needle is inserted into the hip bone to pull the marrow out. The procedure takes between 15 to 30 minutes. The patient is then sent back to the room for about 3 to 4 hours to rest for the next procedureon same day, within the 2 to 4 hours, the stem cells are separated and purified in their stem cell laboratory by using density gradient centrifugation. Once the stem cells have been purified, the patient is taken back to the operation theatre and the stem cells are injected into the spinal space. In some patients, for instance, patients with muscular dystrophy, the stem cells are diluted and injected into the muscles using a very thin needle.One of the participants at the seminar, Marvis Isokpehi, whose child is autistic, had this to say I am glad I came for this seminar. Initially, we were told anything that has to do with brain damage cannot be cured or improved only managed but we see that God helping the scientist, things are getting better. My child was diagnosed by 2. She walked at 17 months, sat at 8 months and she only babbled. She could use her hands and able to put things in her mouth herself but later, the growth began to drop and along the line, I took up the challenge and went back to school to learn about taking care of her and also to help others. I went to Federal College of Education (special) Oyo and specialised in Education for the intellectually disabled. Said Marvis.For Akhere Akran, the Manager of Agatha Obiageli Aghedo Memorial Foundation and participant, one of the arms of our foundation aimed at helping to lessen the burden of the less privileged in the community is the St Agatha Children Centre, where we advocate for children with special needs. I am glad I will be going back to let the parents of these children know there is hope and I am trusting God for funds because that is truly the core of everything. I appeal to the government to fund this and encourage private organisations to help reduce the cost of this treatment to the barest minimum. Its high time we stop stigmatisation or thinking its a result of the mothers past life of the fathers mistakes. It is a medical situation that needs medical attention. Akran expressed.Andelene Thysse is a director at Stem Cell Africa and she helped facilitate the seminar and for her, it is high time Nigeria gets involved We are currently looking at establishing a stem centre at Mozambique. I would have loved that we establish in Nigeria because Nigeria is closer to everything but since we arent getting the audience required, we are going to other African countries interested. Going to NeuroGen Institute for treatment per patient costs about $11,000 imagine if Nigeria has the facility, the price can slash down to $6,000 or even below Andelene stated.Shedding more light on costing, Asok says If we are to set up such a facility in an existing hospital, the cost of setting it up is $US500, 000 and I am assuming all facilities are functioning already. If we have to set up as a whole which includes getting land and building, it will be more expensive. This may sound expensive but it is worth it because it will save you the stress for the future. More important than the money is the permission from the government of the country. The government has to give us the permission because it is what is happening in other African countries. We have had good response and cooperation from government in Kenya, South Africa and Zimbabwe. We have quite a number of Nigerians who come to us in India for this treatment. We treat 50 patients from around the world per week about 5-10 are from Africa and Nigeria is among this percentage.

Kemi Ajumobi

See more here:
Stem cell therapy: proffering hope for special needs patients ... - BusinessDay (satire) (press release) (registration) (blog)

Acupuncture

Acupuncture is a technique in which practitioners stimulate specific points on the body - most often by inserting thin needles through the skin. It is one of the most effective practices used in traditional Chinese medicine. Acupuncture stimulates nerve fibers to transmit signals to the spinal cord and brain, activating the bodys central nervous system. The spinal cord and brain then release hormones responsible for making us feel less pain while improving overall health. Acupuncture may also: increase blood circulation and body temperature, affect white blood cell activity (responsible for our immune function), reduce cholesterol and triglyceride levels, and regulate blood sugar levels.

Aquatherapy

Aquatic Physical Therapy is the practice of physical therapy in a specifically designed water pool with a therapist. The unique properties of the aquatic environment enhance interventions for patients with neurological or musculoskeletal conditions. Aquatic therapy includes a wide range of techniques allowing patients to improve their balance, muscle strength and body mechanics. Aquatic therapy works to enhance the rehabilitation process and support effectiveness of stem cell treatment.

Epidural Stimulation

Hyperbaric Oxygen Therapy

Hyperbaric Oxygen Therapy (HBOT) is the medical use of oxygen at a level higher than atmospheric pressure. The equipment required consists of pressure chamber, which may be of rigid or flexible construction, and a means of delivering 100% oxygen into the respiratory system. Published research shows that HBOT increases the lifespan of stem cells after injection and provides an oxygen-rich atmosphere for the body to function at optimum levels.

Nerve Growth Factor (NGF)

Nerve growth factor (NGF) is a member of the neurotrophic factor (neurotrophin, NTFS) family, which can prevent the death of nerve cells and has many features of typical neurotransmitter molecules. NGF plays an important role in the development and growth of nerve cells. NGF is synthesized and secreted by tissues (corneal epithelial, endothelial, and corneal stromal cells), and it can be up-taken by sympathetic or sensory nerve endings and then transported to be stored in neuronal cell bodies where it can promote the growth and differentiation of nerve cells.NGF can exert neurotrophic effects on injured nerves and promote neurogenesis (the process of generating neurons from stem cells) that is closely related to the development and functional maintenance and repair of the central nervous system. It is also capable of promoting the regeneration of injured neurons in the peripheral nervous system, improving the pathology of neurons and protecting the nerves against hypoxia (lack of oxygen)/ischemia (lack of blood supply).

Nutrition Therapy

Occupational Therapy

Occupational therapy interventions focus on adapting the environment, modifying the task and teaching the skill, in order to increase participation in and performance of daily activities, particularly those that are meaningful to the patient with physical, mental, or cognitive disorders. Our Occupational Therapists also focus much of their work on identifying and eliminating environmental barriers to independence and participation in daily activities, similar to everyday life.

Physiotherapy

Physical therapy or physiotherapy (often abbreviated to PT) is a physical medicine and rehabilitation specialty that, by using mechanical force and movements, remediates impairments and promotes mobility, function, and quality of life through examination, diagnosis, prognosis, and physical intervention. We combine our PT with stem cells for maximum physical rehabilitation improvements.

Transcranial Magnetic Stimulation

Research has shown that TMS can effectively treat symptoms of depression, anxiety, neurological pain, stroke, spinal cord injuries, autism and more. This procedure is very simple and noninvasive. During the procedure, a magnetic field generator or coil is placed near the head of the person receiving the treatment. The coil produces small electrical currents in the region of the brain just under the coil via electromagnetic induction. This electrical field causes a change in the transmembrane current of the neuron which leads to depolarization or hyperpolarization of the neuron and the firing of an action potential.

Read more from the original source:
Stem Cell Treatment for Spinal Cord Injury - Beike ...

There is truth in the old proverb about apple consumption and medical appointments. Insufficient vitamin C can contribute to leukemia. This observed relationship has now been shown to operate through the regulatory role the vitamin plays in the operation of bone marrow stem cells.

These days messages touting a single ingredient as being capable of curing all ills are more likely to peddleturmeric or cannabis, but a few decades ago it was vitamin C that was hailedas preventing everything from theflu to cancer if you took enough. As exaggerated as most of these claims were, it's certainly true that ascorbate, as it is also known, is vital to our health, sometimes in ways that are still unexplained.

We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we havent fully understood why, said Dr Sean Morrison of Childrens Medical Center Research Institute UT Southwestern. Stem cells clearly played a part, but are so rare in any individual tissue that it is impossible to collect the millions usually used for metabolic analysis. Moreover, most mammals make their own ascorbate, but humans cannot, impeding the use of animal models.

Morrison and his co-authors of a paper published in Nature had to develop new techniques to measure metabolite usage in populations as small as 10,000 stem cells to address the first problem. On applying these techniques the authors discovered each type of blood-forming cell has a distinctive signature to its metabolite consumption. They tackled the second problem using mice that lack ascorbate-producing enzymes.

When given a low vitamin C diet these mice had more, and more active, bone marrow stem cells, increasing blood cell production at the price of higher rates of leukemia. The vitamin C concentration was related to levels of the enzyme Tet2, which regulates blood production. Without enough Tet2, the stem cells behaved like an overheating engine, turning out blood cells at a great rate until they turned cancerous. Something similar is observed when mutations reduce Tet2 production.

The first clinical application of the discovery is for patients with clonal hematopoiesis, a condition that often involves reduced Tet2 production and leukemia. Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement, Morrison said. These patients... need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer.

Since stem cells are much sparser in the rest of the body than in bone marrow it will be even more challenging to extend the research to other cancers.

The ideal dose of vitamin C remains to be established, although a paper, coincidentally published last week, may indicate benefits beyond current recommendations.

Read the original here:
Vitamin C Can Suppress Leukemia Up To a Point | IFLScience - IFLScience

What if one day, we could teach our bodies to self-heal like a lizards tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimers or Parkinsons disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institutes Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

One of the things that that attracted me most to the ASU and the Biodesign CMDB was Haos vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology, Stephanopoulos said.

I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice.

Yans research center uses DNA and other basic building blocks to build their nanotechnology structures only at a scale 1,000 times smaller than the width of a human hair.

Theyve already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physics and the creative imaginations of these budding nano-architects.

Learning from nature

The goal of the Center for Molecular Design and Biomimetics is to usenatures design rulesas an inspiration in advancing biomedical, energy and electronics innovation throughself-assembling moleculesto create intelligent materials for better component control and for synthesis intohigher-order systems, said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeleys Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

Weve learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems, Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity, Stephanopoulos said.

Proof all in the design

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to grab the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal off. To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the materials surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinsons disease.

The patients own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells back in the lab and then direct their growth into specific dopamine-producing neurons before transplantation back to the patient.

People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue, Stupp said. In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that.

In the future, it might be possible to perform this process entirely within the body. The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, and injected into a particular spot. Then the soluble peptide-DNA molecules would be given to the patient to bind to the material and manipulate the proliferation and differentiation of transplanted cells.

Scaling the barriers

One of the future challenges in this area will be to develop materials that can respond better to external stimuli and reconfigure their physical or chemical properties accordingly.

Biological systems are complex, and treating injury or disease will in many cases necessitate a material that can mimic the complex spatiotemporal dynamics of the tissues they are used to treat, Stephanopoulos said.

It is likely that hybrid systems that combine multiple chemical elements will be necessary; some components may provide structure, others biological signaling and yet others a switchable element to imbue dynamic ability to the material.

A second challenge, and opportunity, for regenerative medicine lies in creating nanostructures that can organize material across multiple length scales. Biological systems themselves are hierarchically organized: from molecules to cells to tissues, and up to entire organisms.

Consider that for all of us, life starts simple, with just a single cell. By the time we reach adulthood, every adult human body is its own universe of cells, with recent estimates of 37 trillion or so. The human brain alone has 100 billion cells or about the same number of cells as stars in the Milky Way galaxy.

But over the course of a life, or by disease, whole constellations of cells are lost due to the ravages of time or the genetic blueprints going awry.

Collaborative DNA

To overcome these obstacles, much more research funding and recruitment of additional talent to ASU will be needed to build the necessary regenerative medicine workforce.

Last year, Stephanopoulos research received a boost with funding from the U.S. Air Forces Young Investigator Research Program (YIP).

The Air Force Office of Scientific ResearchYIP award will facilitate Nicks research agenda in this direction, and is a significant recognition of his creativity and track record at the early stage of his careers, Yan said.

Theyll need this and more to meet the ultimate challenge in the development of self-assembled biomaterials and translation to clinical applications.

Buoyed by the funding, during the next research steps, Stephanopoulos wants to further expand horizons with collaborations from other ASU colleagues to take his research teams efforts one step closer to the clinic.

ASU and the Biodesign Institute also offer world-class researchers in engineering, physics and biology for collaborations, not to mention close ties with the Mayo Clinic or a number of Phoenix-area institutes so we can translate our materials to medically relevant applications, Stephanopoulos said.

There is growing recognition that regenerative medicine in the Valley could be a win-win for the area, in delivering new cures to patients and building, person by person, a brand-new medicinal manufacturing industry.

Stephanopoulos recent research was carried out at Stupps Northwesterns Simpson Querrey Institute for BioNanotechnology. The National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant 5R01DE015920) provided funding for biological experiments, and the U.S. Department of Energy, Office of Science, Basic Energy Sciences provided funding for the development of the new materials (grants DE-FG01-00ER45810 and DE-SC0000989 supporting an Energy Frontiers Research Center on Bio-Inspired Energy Science (CBES)).

The paper is titled Instructing cells with programmable peptide DNA hybrids. Samuel I. Stupp is the senior author of the paper, and post-doctoral fellows Ronit Freeman and Nicholas Stephanopoulos are primary authors.

See original here:
Bio-inspired Materials Give Boost to Regenerative Medicine - Bioscience Technology

August 15, 2017

What if one day, we could teach our bodies to self-heal like a lizards tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimers or Parkinsons disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institutes Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

One of the things that that attracted me most to the ASU and the Biodesign CMDB was Haos vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology, Stephanopoulos said.

I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice.

Yans research center uses DNA and other basic building blocks to build their nanotechnology structures only at a scale 1,000 times smaller than the width of a human hair.

Theyve already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physics and the creative imaginations of these budding nano-architects.

The goal of the Center for Molecular Design and Biomimetics is to usenatures design rulesas an inspiration in advancing biomedical, energy and electronics innovation throughself-assembling moleculesto create intelligent materials for better component control and for synthesis intohigher-order systems, said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeleys Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

Weve learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems, Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity, Stephanopoulos said.

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to grab the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal off. To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the materials surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinsons disease.

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Restoring loss: Bio-inspired materials give boost to regenerative medicine - Arizona State University

Q: I read that you can use your own stem cells to rejuvenate worn-out knees. Does this really work?

A: Worn out is a good way to term what happens to the knee joint with prolonged use. Lets look at how this happens, starting with cartilage.

The lower portion of the knee joint (at the tibia) contains shock absorbers called menisci made of cartilage. You have one on the inner portion and another on the outer portion of each knee. The upper portion of the knee joint (at the femur) is lined with cartilage as well. All of this cartilage helps protect the bones at the joint but it doesnt heal or regenerate well due to limited blood supply. When severe, worn cartilage leads to arthritis of the knee. In knee X-rays of people over age 60, 37 percent have shown evidence of arthritis of the knees.

The intriguing thing about stem cells is that they have the ability to become any type of cell that the body needs. The cells used for stem cell injections in the knees are called mesenchymal stem cells, and they can differentiate into bone, fat or cartilage cells. These stem cells can come from the fat cells of your body, from your bone marrow or from the inner lining of your knee joint; theyre then replicated in the laboratory and injected into the knee joint.

Heres what the research shows so far.

In a 2013 study, 32 patients with meniscal tears of the knee were injected with a combination of stem cells, platelet-rich plasma and hyaluronic acid. The study reported improved symptoms and even MRI evidence of meniscal cartilage regeneration.

In a 2014 study, 55 patients who had surgery for meniscal tears of the knees were separated into three groups, with two of the groups receiving stem cell injections. Researchers found that, after six weeks, pain had decreased substantially in the two groups that received stem cell injections and that the decrease was even greater at one and two years after the injection.

In a 2017 study in the British Journal of Sports Medicine, researchers analyzed six studies that used stem cells for osteoarthritis of the knees. In five of the studies, stem cells were given after surgery to the knee; in the other study, stem cells from a donor were administered without surgery. All the studies showed reduced pain and improved knee function. Further, in three of the four trials, MRIs corroborated the cartilage improvements.

There may be benefit to stem cell injections for cartilage loss of the knees, but more data are needed. Id also like to see more data on this type of therapy as a preventive measure for younger patients before their knees are worn out.

ASK THE DOCTORS is written by Robert Ashley, M.D., Eve Glazier, M.D., and Elizabeth Ko, M.D. Send questions to askthedoctors@

mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095.

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Stem cell therapy may help knees - Citizens Voice

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

Continued here:
Unexpected fountain of youth found in cardiac stem cells ...

DETROIT Near the open doorway in the Comerica Park visitors clubhouse is a sign warning the curious to stay out of the kitchen. No media, it reads, making its point in all caps. So, its with some irony that a few feet away, Bartolo Coln agrees to a brief one-on-one with a reporter, his first since joining the Minnesota Twins.

Coln has fulfilled his media requirements when he starts, speaking with reporters through Twins interpreter Carlos Font about his performances, but thats where he prefers to leave it. Hes easy to find in the clubhouse, and will say hello and shake your hand, but he also makes it clear that its not going any further which would be fine if he hadnt become an essential part of the Twins playoff chase.

When the Twins signed Coln to a minor league deal on July 7, the primary response was laughter. This is the help the American League Centrals surprise team is getting for the stretch run, a 44-year-old with a 2-8 record and 8.14 earned-run average who had just been given his outright release by the Atlanta Braves?

Well, no ones laughing now.

I think it probably raised a few eyebrows when we brought him in, but hes been valuable, manager Paul Molitor said.

What appears to be happening is another in a string of career resurrections for the right-hander who broke in with the Cleveland Indians in 1997, won a Cy Young Award in 2005 and signed his first free-agent minor league deal with Boston in 2008. Hes no longer throwing hard, but his control remains as sharp as his competitive nature.

The older I get, the more I want to play, he said.

Over his past three starts, Coln is 2-0 with a 2.82 ERA with three walks and 11 strikeouts in 22.1 innings pitched. In his last start, he became the oldest AL pitcher to throw a complete game since Hall of Famer Nolan Ryan did it for Texas in 1992. On Tuesday, hell make the most important start of the season so far in the opener of a three-game series against the first-place Cleveland Indians at Target Field.

That explains the persistence that has kept alive a career that has seemed dead more than once. It was a whopping nine years ago that Coln first signed a minor league deal with a spring training invite, a cheap gambit by the Boston Red Sox. In four seasons from 2006-09, he went 14-21 with a 5.18 ERA with three clubs while batting elbow and shoulder problems. He missed all of 2010.

I thought I was going to be done, he said.

Coln credits 2010 stem-cell treatment fat and bone marrow was re-injected into his elbow and shoulder for saving his arm. Major League Baseball studied the treatment to see if it fell under its performance-enhancing drug policy, but it has since become a popular, if not quite trumpeted, treatment for pitchers hoping to avoid reconstructive surgery.

It has helped me to keep my arm young and keep me going, Coln said.

Coln, however, did fall afoul of MLB when he tested positive for testosterone in August 2012. He was 39, and many suspected had finally hit the end of the road. Yet, he returned the next season with Oakland and went 18-6 with a 2.65 ERA and an AL-best three shutouts.

Last season, he went 15-8 with a 3.34 ERA with the Mets, parlaying the season into a one-year, $12.5 million deal with Atlanta. The Braves are still on the hook for most of that contract, meaning the Twins are getting Coln at a bargain, prorated league minimum roughly $220,000.

He chose the Twins over the Mets after receiving a call from friend and former teammate in Anaheim, Ervin Santana.

The Mets and the Twins were the teams requesting my services, and I was weighing my options, Coln said. Ervin Santana called me and asked me to come and told me how good the organization was, how good the team was. After I started looking at it, and seeing how young their pitching was and how many young kids we had on the team, and I thought its not only an opportunity for me to pitch, but an opportunity to teach other young players how to pitch and how to be big-leaguers.

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Twins' Bartolo Coln: 'The older I get, the more I want to play.' - Winona Daily News