Third in an occasional series on how Harvard researchers are tackling the problematic issues of aging.

If only, wrote an ancient Japanese poet, when one heard that Old Age was coming one could bolt the door.

Science is working on it.

Aging is as much about the physical processes of repair and regeneration and their slow-motion failure as it is the passage of time. And scientists studying stem cell and regenerative biology are making progress understanding those processes, developing treatments for the many diseases whose risks increase as we get older, while at times seeming to draw close to a broader anti-aging breakthrough.

If stem cells offer potential solutions, theyre also part of the problem. Stem cells, which can differentiate into many cell types, are important parts of the bodys repair system, but lose regenerative potency as we age. In addition, their self-renewing ability allows the mutations that affect every cell to accumulate across cellular generations, and some of those mutations lead to disease.

We do think that stem cells are a key player in at least some of the manifestations of age, said Professor of Stem Cell and Regenerative Biology David Scadden, co-director of the Harvard Stem Cell Institute. The hypothesis is that stem cell function deteriorates with age, driving events we know occur with aging, like our limited ability to fully repair or regenerate healthy tissue following injury.

When it comes to aging, certain tissue types seem to lead the charge, according to Professor of Stem Cell and Regenerative Biology Lee Rubin, who directs the Harvard Stem Cell Institutes Therapeutic Screening Center. Particular tissues nerve cells appear to be one somehow signal to others that its time to age. This raises the prospect, Rubin said, that aging might be reversed by treating these key tissue categories, rather than designing individual treatments for the myriad tissue types that make up the body.

The process of aging involves all tissues in your body and, while different things go wrong in each tissue, they go wrong at basically the same rate, Rubin said. We can think of it as a process that is somehow coordinated, or there are fundamental processes in each tissue that play out.

In addition to key tissues, certain chemical pathways like insulin signaling seem to be able to control aging, said Rubin, whose work has received backing from the National Institute of Neurological Disorders and Stroke, as well as private foundations. The insulin signaling pathway is a chemical chain reaction in which the hormone insulin helps the body metabolize glucose. Reducing it has been shown to greatly extend life span in flies and worms, Rubin said. Also, signaling doesnt have to be reduced in all tissues.

If you just reduce it in neurons, the whole fly or worm lives longer, Rubin said. Certain key tissues in those organisms, if you selectively manipulate those tissues, have a positive effect on a number of processes in other tissues.

Because it circulates throughout the body, blood is an obvious place to look for controlling or signaling molecules that prompt or coordinate aging. A key carrier of oxygen and nutrients, blood is also rich with other compounds, some of which appear to play a role in decline linked to age.

Scadden described recent work done separately by Ben Ebert, a professor of medicine working at Harvard-affiliated Brigham and Womens Hospital, and Steve McCarroll, the Dorothy and Milton Flier Associate Professor of Biomedical Science and Genetics, that identified age-related changes in the blood that can increase the risk of diseases we dont typically think of as blood diseases.

Another tantalizing study, published in 2013, used the blood of a young mouse to rejuvenate the organs of an older one. In these parabiotic experiments, conducted by Professor of Stem Cell and Regenerative Biology Richard Lee and Forst Family Professor of Stem Cell and Regenerative Biology Amy Wagers, the circulatory systems of the two mice were joined, allowing the blood of the young to flow through the older ones body. The older mouse showed improvements in muscle tone and heart function. Later, similar experiments done by Rubin also showed improvements in neuronal health and brain functioning.

The young mouses fate depended on the age of the older mouse, Rubin said. If the latter was middle-aged, the young mouse appeared to be fine. If the older mouse was very old, however, the young mouse did worse.

Rubin said the experiments suggest that blood contains both positive and negative factors that influence aging. It may be, he said, that both are always present, but that positive factors outweigh negative in the young and that negative factors increase as we age.

Researchers have identified but not yet confirmed candidate blood factors for the rejuvenating effects. What seems not in doubt is the overall effect of the young blood on the old mouse. Interest is intense enough that a California company, Alkahest, has begun experiments giving Alzheimers patients plasma from young blood in hopes of improving cognition and brain function.

Even if that approach works, Rubin said, there would be practical hurdles to the widespread administration of young peoples blood plasma to older patients. But with an active compound identified, a drug could be made available to restore at least some cognitive function in Alzheimers patients.

In addition to the overall process of aging, researchers at the Harvard Stem Cell Institute, as well as across the University and its affiliated institutions, are investigating an array of diseases whose incidence increases sometimes dramatically with age.

The list includes several of the countrys top causes of death heart disease, stroke, diabetes, and cancer as well as rarer conditions such as the lethal neurodegenerative disorder amyotrophic lateral sclerosis (ALS).

Two decades ago, when stem cell research hit mainstream consciousness, many thought its greatest promise would be in stem cells ability to grow replacement parts: organs and tissues for damage caused by trauma or disease.

The stem cell revolution is still developing, Scadden said, but so far has taken a different form than many expected. The dream of harnessing stem cells to grow replacement hearts, livers, and kidneys remains, but potentially powerful uses have emerged in modeling disease for drug discovery and in targeting treatment for personalized medicine.

We thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

David Scadden

Researchers have taken from the sick easily accessible cells, such as skin or blood, and reprogrammed them into the affected tissue type nerve cells in the case of ALS, which most commonly strikes between 55 and 75, according to the National Institutes of Health (NIH).

These tissues are used as models to study the disease and test interventions. Work on ALS in the lab of Professor of Stem Cell and Regenerative Biology Kevin Eggan has identified a drug approved for epilepsy that might be effective against ALS. This application is now entering clinical trials, in collaboration with Harvard-affiliated Massachusetts General Hospital.

In the end, stem cells might have their greatest impact as a drug-discovery tool, Scadden said.

Much of stem cell medicine is ultimately going to be medicine, he said. Even here, we thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

Also evolving is knowledge of stem cell biology. Our previous understanding was that once embryonic stem cells differentiated into stem cells for muscle, blood, skin, and other tissue, those stem cells remained flexible enough to further develop into an array of different cells within the tissue, whenever needed.

Recent work on blood stem cells, however, indicates that this plasticity within a particular tissue type may be more limited than previously thought, Scadden said. Instead of armies of similarly plastic stem cells, it appears there is diversity within populations, with different stem cells having different capabilities.

If thats the case, Scadden said, problems might arise in part from the loss of some of these stem cell subpopulations, a scenario that could explain individual variation in aging. Getting old may be something like the endgame in chess, he said, when players are down to just a few pieces that dictate their ability to defend and attack.

If were graced and happen to have a queen and couple of bishops, were doing OK, said Scadden, whose work is largely funded through the NIH. But if we are left with pawns, we may lose resilience as we age.

Scaddens lab is using fluorescent tags to mark stem cells in different laboratory animals and then following them to see which ones do what work. It might be possible to boost populations of particularly potent players the queens to fight disease.

Were just at the beginning of this, Scadden said. I think that our sense of stem cells as this highly adaptable cell type may or may not be true. What we observe when we look at a population may not be the case with individuals.

The replacement parts scenario for stem cells hasnt gone away. One example is in the work of Harvard Stem Cell Institute co-director and Xander University Professor Douglas Melton, who has made significant progress growing replacement insulin-producing beta cells for treatment of diabetes.

Another is in Lees research. With support from the NIH, Lee is working to make heart muscle cells that can be used to repair damaged hearts.

Trials in this area have already begun, though with cells not genetically matched to the patient. In France, researchers are placing partially differentiated embryonic stem cells on the outside of the heart as a temporary aid to healing. Another trial, planned by researchers in Seattle, would inject fully differentiated heart muscle cells into a patient after a heart attack as a kind of very localized heart transplant.

Lees approach will take longer to develop. He wants to exploit the potential of stem cell biology to grow cells that are genetically matched to the patient. Researchers would reprogram cells taken from the patient into heart cells and, as in the Seattle experiment, inject them into damaged parts of the heart. The advantage of Lees approach is that because the cells would be genetically identical to the patient, he or she could avoid antirejection drugs for life.

What were thinking about is longer-term but more ambitious, Lee said. Avoiding immune suppression could change the way we think about things, because it opens the door to many decades of potential benefit.

Change has been a constant in Lees career, and he says theres no reason to think that will slow. Patient populations are older and more complex, disease profiles are changing, and the tools physicians have at their disposal are more powerful and more targeted.

Many of our patients today wouldnt be alive if not for the benefit of research advances, he said. Cardiology has completely changed in the last 25 years. If you think its not going to change even more in the next 25 years, youre probably wrong.

When Lee envisions the full potential of stem cell science, he sees treatments and replacement organs with the power to transform how we develop and grow old.

It may not be there for you and me, but for our children or their children, ultimately, regenerative biology and stem cell biology have that kind of potential, he said. We imagine a world where it doesnt matter what mutations or other things youre born with, because we can give you a good life.

Lees not guessing at future longevity. Hes not even sure extending life span beyond the current record, 122, is possible. Instead, he cites surveys that suggest that most Americans target 90 as their expectation for a long, healthy life.

Thats about a decade more than we get now in America, Lee said. We have work to do.

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Researchers study secrets of aging via stem cells - Harvard Gazette

Skin Stem Cells Comments Off on Researchers study secrets of aging via stem cells – Harvard Gazette | April 18th, 2017

MADISON, Wis.--(BUSINESS WIRE)--

Cellular Dynamics International (CDI), a FUJIFILM company and a leading developer and manufacturer of induced pluripotent stem cell-derived products, today announced it has signed a distribution agreement with STEMCELL Technologies, a world leader in iPS cell culture media.

This joint agreement with STEMCELL Technologies will make iPSC technology widely available to researchers worldwide, helping advance biological research leading to cellular therapies and drug discovery, said Dr. Bruce Novich, Division President-CNBD for FUJIFILM Holdings America Corporation and Executive Vice President and General Manager for CDI. We believe that STEMCELL Technologies, a leading developer, manufacturer and seller of stem cell related products, is an ideal partner for CDI, because their global sales and distribution infrastructure delivers to an established and an emerging customer base, which translates into faster access to and deeper penetration of CDIs leading edge technologies and products.

Under the terms of the agreement, STEMCELL Technologies will distribute CDIs iCell catalog of products in North America, Europe, and Singapore, with other countries under consideration. CDIs iCell products are differentiated human induced pluripotent stem cell (iPSC)-derived cells, which include cardiomyocytes, hepatocytes, and others, totaling up to 12 cell types.

STEMCELL Technologies is delighted for the opportunity to bring CDIs innovative products to the global research community. STEMCELL and CDI will work together on progressive solutions for the life science tools market. We look forward to a long and productive partnership with the shared goal of improving human health, said Dr. Allen Eaves, President and CEO of STEMCELL Technologies.

About Cellular Dynamics International:

Cellular Dynamics International (CDI), a FUJIFILM company, is a leading developer and supplier of human cells used in drug discovery, toxicity testing, and regenerative medicine applications. Leveraging technology that can be used to create induced pluripotent stem cells (iPSCs) and differentiated tissue-specific cells from any individual, CDI is committed to advancing life science research and transforming the therapeutic development process in order to fundamentally improve human health. The companys inventoried iCell products and donor-specific MyCell Products are available in the quantity, quality, purity, and reproducibility required for drug and cell therapy development. For more information please visit http://www.cellulardynamics.com.

About Fujifilm

FUJIFILM Holdings Corporation, Tokyo, Japan brings continuous innovation and leading-edge products to a broad spectrum of industries, including: healthcare, with medical systems, pharmaceuticals and cosmetics; graphic systems; highly functional materials, such as flat panel display materials; optical devices, such as broadcast and cinema lenses; digital imaging; and document products. These are based on a vast portfolio of chemical, mechanical, optical, electronic, software and production technologies. In the year ended March 31, 2016, the company had global revenues of $22.1 billion, at an exchange rate of 112.54 yen to the dollar. Fujifilm is committed to environmental stewardship and good corporate citizenship. For more information, please visit: http://www.fujifilmholdings.com.

About STEMCELL Technologies:

As Scientists Helping Scientists, STEMCELL Technologies is committed to providing high-quality cell culture media, cell isolation products, accessory tools and educational services for life science research. Driven by science and a passion for quality, STEMCELL provides over 2500 products to more than 90 countries worldwide. To learn more, visit http://www.stemcell.com.

All product and company names herein may be trademarks of their registered owners.

View source version on businesswire.com: http://www.businesswire.com/news/home/20170418005219/en/

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Cellular Dynamics International Signs Distribution Deal with STEMCELL Technologies - Yahoo Finance

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April 17, 2017 by Hannah L. Robbins SMN protein (red) is necessary for the survival of spinal cord neurons (motor neurons) responsible for breathing and all movement. Harvard researchers have found a compound that stabilized this protein in mouse and human motor neurons. This may lead to the development of new treatments for motor neuron diseases including Spinal Muscular Atrophy and Lou Gehrigs disease. Credit: Natalia Rodriguez-Muela

Harvard Stem Cell Institute (HSCI) researchers have identified a compound that helps protect the cells destroyed by spinal muscular atrophy (SMA), the most frequent fatal genetic disease in children under 2 years of age.

SMA is a neurodegenerative disease targeting motor neurons, the long nerve cells that relay messages from the brain to the muscles and that are, consequently, responsible for bodily movements, including walking, swallowing, and even breathing. Patients with milder forms of SMA experience muscle wasting that may confine them to a wheelchair, while the more severe forms cause paralysis and death before the second birthday.

About one in 50 people are genetic carriers of the disease.

Because of a dysfunctional gene, many motor neurons in SMA patients are unable to produce adequate amounts of a protein called survival of motor neuron (SMN). The deficiency causes cellular stress and eventually cell death. Rather than fixing the gene, which has been the strategy of many labs looking to develop SMA therapies, the Harvard team has identified a compound that helps stabilize the SMN protein both in human neurons in a dish and in mouse models.

The findings were published in the journal Cell Reports.

"This discovery opens up new lines of drug interrogation," said Lee Rubin, HSCI principal faculty member and the senior author on the study. Rubin's lab, which operates out of in Harvard's Department of Stem Cell and Regenerative Biology, uses induced pluripotent stem cells (iPS cells) to make human models of neurological diseases.

In 2015, Rubin made a variety of neuronal types from the iPS cells of SMA patients in order to determine why motor neurons in particular were targeted, and found they experienced a fatal stress response similar to motor neurons affected by amyotrophic lateral sclerosis (ALS), the late-onset neurodegenerative disease more commonly known as Lou Gehrig's disease.

Additionally, some SMA-affected motor neurons were dying before others, though all of the neurons had the same genetic mutations and were experiencing the same stressful environment.

"Clearly, some motor neurons were surviving, so the next question was whether this is random or if there is a molecular explanation," Rubin said.

Early on in their most recent study, the researchers found that within a single petri dish of motor neurons derived from an SMA patient, some produced up to four times as much SMN protein as their neighbors. Over time, those motor neurons with higher levels of SMN were more likely to survive after exposure to toxic environments and stressors.

When the team analyzed motor neurons derived from ALS patients, they found similar results: Motor neurons with higher levels of SMN were likelier to survive than those with lower levels.

"The surprise was when we looked in a control culture and also saw differences between the individual neurons," Rubin said.

"It is clear that the SMN protein is necessary for all motor neuron survival, not just motor neurons targeted by ALS or SMA," said Natalia Rodrguez-Muela, a postdoctoral fellow in Rubin's lab and co-first author on the paper. The results suggest that if the team could increase the amount of SMN protein in any single motor neuron, they would be able to rescue the cell.

During a cell's life span, proteins are constantly being made and degraded, made and degraded again. To interrupt the process of breaking down the SMN protein, the researchers looked at a family of proteins called Cullins, which act as a part of the cell machinery that regulates protein degradation.

In 2011, the Rubin lab had determined that an enzyme called GSK3b helps control SMN stability. Nearly all proteins degraded by GSK3b are flagged for degradation by a pathway that involves a specific member of the Cullin family. Rubin said the researchers hypothesized that if they could block that Cullin-mediated process, the SMN proteins would not be flagged for degradation and would remain stable longer.

The researchers, led by co-first author Nadia Litterman, then dosed human and murine motor neurons with a compound known to block the specific Cullin and found that exposure to the compound made SMN proteins more stable and more abundant. As a consequence, the compound promoted survival of all motor neurons, both in human cells in the dish and in mouse models.

Additionally, mice with SMA, even the more severe forms of the disease, had some of their symptoms improve after exposure to the compound.

"This process points to an unexplored therapeutic direction that could benefit patients of not one, but two separate diseases," Rubin said.

Explore further: Hope against disease targeting children

More information: Natalia Rodriguez-Muela et al. Single-Cell Analysis of SMN Reveals Its Broader Role in Neuromuscular Disease, Cell Reports (2017). DOI: 10.1016/j.celrep.2017.01.035

Journal reference: Cell Reports

Provided by: Harvard University

This story is published courtesy of the Harvard Gazette, Harvard University's official newspaper. For additional university news, visit Harvard.edu.

Harvard Stem Cell Institute (HSCI) researchers studying spinal muscular atrophy (SMA) have found what they term "surprising similarities" between this childhood disorder that attacks motor neurons and amyotrophic lateral ...

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Harvard Stem Cell Institute (HSCI) researchers have identified a compound that helps protect the cells destroyed by spinal muscular atrophy (SMA), the most frequent fatal genetic disease in children under 2 years of age.

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Scientists find evidence that ALS and SMA could be treated with a ... - Medical Xpress

Spinal Cord Stem Cells Comments Off on Scientists find evidence that ALS and SMA could be treated with a … – Medical Xpress | April 17th, 2017

Photo courtesy of the University of Minnesota

MINNEAPOLIS/ST. PAUL A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack.

The research study was published Apr. 14 inCirculation Research, a journal published by the American Heart Association. Researchers have filed a patent on the discovery.

According to the American Heart Association, heart disease is the No. 1 cause of death in the U.S. killing more than 360,000 people a year. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die. Our bodies cant replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure.

In this study, researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

Watch a video of the cells beating on the patch.

Video credit:College of Science and Engineering, UMN

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries.

Related Article:3D-Printed Guide Helps Regrow Complex Nerves After Injury

This is a significant step forward in treating the No. 1 cause of death in the U.S., said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years.

A team of biomedical engineering researchers has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. Two of the researchers involved are biomedical engineering associate professor Brenda Ogle (right) and PhD student Molly Kupfer (left).Photo credit: Patrick OLeary, University of MinnesotaOgle said that this research is different from previous research in that the patch is modeled after a digital, three-dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells. Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue.

We were quite surprised by how well it worked given the complexity of the heart, Ogle said. We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch.

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart.

The research was funded by the National Science Foundation, National Institutes of Health, University of Minnesota Lillehei Heart Institute, and University of Minnesota Institute for Engineering in Medicine.

In addition to Ogle, other biomedical engineering researchers who were part of the team include Molly E. Kupfer, Jangwook P. Jung, Libang Yang, Patrick Zhang, and Brian T. Freeman from the University of Minnesota; Paul J. Campagnola, Yong Da Sie, Quyen Tran, and Visar Ajeti from the University of Wisconsin-Madison; and Jianyi Zhang, Ling Gao, and Vladimir G. Fast from the University of Alabama,

To read the full research paper entitled Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold, visit theCirculation Researchwebsite.

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3D-Printed Patch Can Help Mend a 'Broken' Heart - Lab Manager | News (press release) (blog)

Cardiac Stem Cells Comments Off on 3D-Printed Patch Can Help Mend a ‘Broken’ Heart – Lab Manager | News (press release) (blog) | April 17th, 2017

BROOMFIELD, Colo., April 17, 2017 /PRNewswire/ -- "Interventional orthopedics in pain medicine practice" was recently published by Elsevier as a chapter in Techniques in Regional Anesthesia and Pain Management. The chapter, authored by Regenexx founder Christopher J. Centeno, MD examines less invasive ways to treat orthopedic pain and injuries through autologous biologics, such as stem cells and platelet rich plasma (PRP), and the shift from surgical orthopedics to interventional orthopedics.

Interventional orthopedics utilizing advanced technologies, such as ultrasound and X-ray guidance, precise percutaneous injections of autologous biologics, and bone marrow concentrate, (BMC) expand nonsurgical options in the field of orthopedics. Citing the dramatic reduction in cardiac surgery rates since the adoption of the specialty interventional cardiology, the authors reveal, "We are poised on the brink of the same change in orthopedic care." The authors also state, "The field of autologous biologics has the potential to alter the playing field of orthopedic care by allowing percutaneous injections to replace the need for more invasive orthopedic surgeries."

The chapter covers three important tenets in the developing field that will allow Interventional Orthopedics to alter traditional orthopedic care in the future. First is the rapid expansion of injectates (material being injected), such as stem cells and PRP, that can help heal damaged tissue and that can effectively treat musculoskeletal tissues. Second is the precise image-guided placement of those injectates into those damaged tissues. And third is the development of new tools that will advance this regenerative-medicine technology. The chapter also highlights research that supports the use of bone marrow stem cells and the importance of education standards and organization, training, and retraining of physicians to meet these standards.

The full chapter "Interventional orthopedics in pain medicine practice" can be found online at http://www.sciencedirect.com/science/article/pii/S1084208X16300052.

Christopher J. Centeno, MD, is the CEO of Regenexx and an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. Dr. Centeno maintains an active research-based practice and has multiple publications listed in the US National Library of Medicine.He has also served as editor-in-chief of a medical research journal dedicated to traumatic injury and is one of the few physicians in the world with extensive experience in the culture expansion of and clinical use of adult stem cells to treat orthopedic injuries.

MEDIA CONTACT Mark Testa 155014@email4pr.com (303) 885-9630

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/regenexx-network-using-regenerative-medicine-technologies-in-interventional-orthopedics-to-treat-pain-300439851.html

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Regenexx Network Using Regenerative Medicine Technologies in Interventional Orthopedics to Treat Pain - Yahoo Finance

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The prognosis was dire when Cheryl Grantham learned she had multiple myeloma, a rare form of cancer, in March 1999.

"I thought I'd be dead by Christmas," she said.

The best treatment to extend her life was a round of specialty high-dose chemotherapy, a course more potent than the normal chemotherapy prescribed to combat more common cancers.

Multiple myeloma is cancer of the plasma cells and the high-dose chemotherapy treatments fight it by destroying the cancerous cells in the bone marrow, where plasma originates. The treatments are intense enough that it can kill a patient. But it's one of the most effective ways to treat the cancer.

So doctors a few decades ago created a workaround using stem cells, extracting them from the patient's blood before administering the high-dose chemotherapy and then transplanting them back in to repair the damaged bone marrow after the chemo has been given.

Stem cells are given back to the patient like a blood transfusion, saidBrock Whittenberger, Grantham's doctor at Billings Clinic.

Billings Clinic has been using this stem cell approach with its myeloma cancer treatments for years, and Whittenberger has been the one performing procedure.

"What it's allowed us to do is successfully treat the cancer," he said. "There's a fairly rapid recovery."

Billings Clinic was recently accredited by the Foundation for the Accreditation of Cellular Therapy for its stem cell treatment.With the FACT accreditation, those treatments will be more accessible.

The accreditation also will make it easier for insurance companies to approve the procedure and will allow Billings Clinic to conduct trials on the stem cell treatment.

Billings Clinic is currently the only FACT-accredited center in Montana.

Grantham, who was an infusion nurse at the time of her diganosis, elected to have the treatment and has outlived her initial prognosis by almost two decades.

"I've been fine," she said. "I've been alive for 18 years."

Unexpectedly, the treatments helped her become a better nurse.

"It made me more empathetic," she said.

The stem cell treatment eradicates certain forms of lymphoma but it won't cure Grantham's cancer. At some point themultiple myeloma will return.

Until then, she visits with her doctor every three months for blood work and works to keep her focus on the now.

"With a diagnosis like that you have short-term goals," she said.

Her youngest son was in high school in 1999, and she was still working full time as a nurse. As much as she wanted to crawl under her covers and not face the reality of her cancer diagnosis, she had no choice but to move forward.

"It made me be normal," she said.

And it helped her focus on what was important in the moment. The Christmas before she began her treatments, she took her three sons to the Cayman Islands for the holidays.

"Because everything was going to change," she said."You just do it."

And it's an attitude she still carries. Her youngest son, long graduated from high school, is now married. These days, she's hopeful he'll give her a grandchild.

"That's my goal now," she said, smiling.

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Billings Clinic accredited for using stem cell method to 'successfully treat' a rare cancer - Billings Gazette

Bone Marrow Stem Cells Comments Off on Billings Clinic accredited for using stem cell method to ‘successfully treat’ a rare cancer – Billings Gazette | April 17th, 2017

On March 13th, Sarina Vito, an 18-year-old from Elwood, was preparing to spend a weekend away with her mother ather very first orientation as an incoming fall freshman at High Point University in North Carolina.

Instead, the John Glenn High School seniors entire world was flipped upside down bya devastating phone call: Sarina was diagnosed with acute myeloid (AML) leukemiaa cancer characterized by the production of a large number of abnormal white blood cells inthe bone marrow.

Sarina was immediately admitted into the Cohen Childrens Medical Center, where shewill require a lifesaving bone marrow/stem cell transplant after her third round of chemotherapy. She will also have to undergo fertility treatments in order to be able to have children of her own.

To help Sarina find her donor match as well as raise awareness and much-needed funds for not just her and her familys battle with this disease, but also for childhood cancer foundations, her family, friends and the Elwood community are holding a bone marrow drive and fundraiser at John Glenn High School on Tuesday, April 25, from 4 p.m. to 8:30 p.m. (Scroll down for official flier.)

This Bone Marrow Registry Drive & Sarinas Strands of Strength Ponytail Drive will include bone-marrow test swabbing provided by Be The Match Foundation, a bake sale, a raffle with prizes, vendor tables, music by Tony Bruno, and hair extensions by Cactus Salons. Among its proud supporters: Be The Match Foundation, Mondays at Racine, Hair We Share and Cactus Salon.

The Sarina Strong Fund also has a GoFundMe Page collecting donations.

Although Sarina will be missing many things that she worked very hard for, this event will help her and her family in many other ways. As the organizers of this benefit understand, no family should have to suffer the devastating emotional, mental and financial strains a disease such as AML leukemia causes them, especially not alone.

Consider this post an open invitation for local businesses and members of the Long Island community to contribute and lend support by donating baskets, gift certificates, services, raffle prizes, food and/or refreshments, become a sponsor with monetary donations, or simply help spread the wordthats why a special hashtag #SarinaStrong has been created to help raise awareness across social media; spread it far and wide!

Sarina and her family thank you in advance: Together, we can do this!

Featured Photo: The Elwood Community is hosting the #SarinaStrong Bone Marrow Registry Drive & Fundraiser for Sarina Vito, 18, who is battling AML leukemia, at John Glenn High School in Elwood, on April 25, 2017. (Photo: #SarinaStrong GoFundMe page)

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Bone Marrow Drive & Fundraiser To Support Sarina Vito, 18, Battling Leukemia - Long Island Press

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Last year, the Centers for Medicare and Medicaid Services enacted a significant policy change improving access to blood and marrow transplants for Medicare patients diagnosed with life-threatening blood cancers. The change came in the form of a Medicare rule on how outpatient blood and marrow transplants are reimbursed by the federal health care program beginning on Jan. 1, 2017.

While this move a step in the right direction, this rule does not address the vast majority of transplants (97 percent) that are performed in the inpatient setting. Sadly, Medicare continues to provide inadequate reimbursement to hospitals performing inpatient transplants and this limitation threatens to limit access to seniors needing this lifesaving therapy.

It is estimated that a new patient is diagnosed with a blood cancer every three minutes. More than 170,000 Americans will receive a blood cancer diagnosis like leukemia, lymphoma or myeloma this year alone; approximately 1.2 million Americans currently live with these diseases.

Blood and marrow transplants using a donor (allogeneic transplants) remain the only curative treatment for many blood cancers. The process of transplantation typically involves treating the patient with chemotherapy and then restoring healthy cells in the recipient by an infusion of blood or bone marrow stem cells, obtained from a matched related or unrelated donor or from umbilical cord blood. These donor cells also help to eliminate any cancer cells that survive chemotherapy.

The fatal blood diseases that require transplants occur most commonly in older individuals, who are also most likely to be covered by Medicare. Historically, the risks of transplant were too great to allow us to safely transplant many seniors. However, rapid clinical advances have resulted in dramatically improved outcomes in older adults. In fact, patients over the age of 65 are now the most rapidly growing population in U.S. transplant centers.

Despite the overwhelming clinical evidence demonstrating the curative potential of transplants in older patients, transplant access for seniors is threatened by Medicares chronic underfunding for both the transplant itself and the costs required to obtain matched bone marrow or cord blood. Medicare, for the most part, adequately reimburses transplants of solid organs such as hearts and lungs, appropriately covering the costs of acquiring those organs.

Surprisingly, Medicare treats the cost of acquiring bone marrow differently. Currently, Medicare pays for the cost of acquiring bone marrow and the transplant procedure and hospitalization in a single payment. Unfortunately, the amount currently reimbursed falls well short of the costs of providing the complex care required for blood and marrow transplant recipients, who are vulnerable to complications including infections in the post-transplant period. Unlike solid organ transplants, the cost of obtaining unrelated donor blood, bone marrow or cord blood is not directly and completely reimbursed.

This inadequate reimbursement threatens the ability of transplant centers to continue to take on the complex care of seniors with blood cancers. Unless reimbursement policies change, some seniors may face limited access to their only curative treatment option.

Thanks to national investment in research and continued innovation, seniors diagnosed with cancer today have more treatment options than they had in the past. Poor federal reimbursement policies must be updated to provide patients with access to the treatments that offer them the best possible outcomes, including transplantation.

While last years policy change was a marked improvement in reimbursement for those three percent of transplants occurring in the outpatient setting, it is important that similar payment reforms now address themajority of blood and marrowtransplants that are performed as inpatient procedures.

I urge Medicare to revise its payment policies for blood and marrow transplants to strengthen reimbursement in the inpatient hospital setting to ensure American seniors the full range of life-saving treatment options for cancer that they deserve.

Krishna Komanduri is president of the American Society for Blood and Marrow Transplantation and the Kalish Family Chair in Stem Cell Transplantation, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.

Morning Consult welcomes op-ed submissions on policy, politics and business strategy in our coverage areas. Updated submission guidelines can be foundhere.

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Ensure Medicare Access to Blood and Marrow Transplants for Seniors with Cancer - Morning Consult

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A research team at University of Wisconsin School of Medicine and Public Health has treated its first patient in an innovative clinical trial using stem cells for the treatment of heart failure that develops after a heart attack.

The trial is taking place at University Hospital, one of three sites nationwide currently enrolling participants. The investigational CardiAMP therapy is designed to deliver a high dose of a patients own bone-marrow cells directly to the point of cardiac injury to potentially stimulate the bodys natural healing response.

The patient experience with the trial begins with a cell-potency screening test. Patients who qualify for therapy are scheduled for a bone-marrow aspiration. The bone marrow is then processed on-site and subsequently delivered directly to the damaged regions in a patients heart in a minimally invasive procedure.

Patients living with heart failure experience a variety of negative symptoms that can greatly impact their day-to-day life, said UW Health cardiologist Dr. Amish Raval, associate professor of medicine and one of the principal investigators for the trial. By being at the forefront of research for this debilitating condition, we look forward to studying the potential of this cell therapy to impact a patients exercise capacity and quality of life.

The primary outcome to be measured is the change in distance during a six-minute walk 12 months after the initial baseline measurement.

Heart failure commonly occurs after a heart attack, when the heart muscle is weakened and cannot pump enough blood to meet the body's needs for blood and oxygen. About 790,000 people in the U.S. have heart attacks each year. The number of adults living with heart failure increased from about 5.7 million (2009-2012) to about 6.5 million (2011-2014), and the number of adults diagnosed with heart failure is expected to dramatically rise by 46 percent by the year 2030, according to the American Heart Association (AHA).

The CardiAMP Heart Failure Trial is a phase III study of up to 260 patients at up to 40 centers nationwide. Phase III trials are conducted to measure effectiveness of the intervention, monitor side effects and gather information for future use of the procedure. Study subjects must be diagnosed with New York Heart Association (NYHA) Class II or III heart failure as a result of a previous heart attack.

Information about eligibility or enrollment in the trial is available at http://www.clinicaltrials.gov, or through a cardiologist.

The trial is funded by Biocardia, Inc., which developed the potential therapy.

Date Published: 04/17/2017

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UW Treats First Participant in Trial of Stem-Cell Therapy for Heart Failure - University of Wisconsin-Madison

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CHEYENNE Had it not been for a single bone marrow transplant, the Day of Giving would never have started.

Its a bone marrow transplant that saved founder Greta Morrows life, and what inspired her to launch a community charity event that encourages, among other things, the importance of donating blood, tissue, bone marrow and organs.

Greta is a prime example of somebody who is a survivor because of someone being on the bone marrow donation registry, said Caroline Veit, a longtime Day of Giving volunteer and a past president for the event. Its life saving. When somebody is at the end of their treatment options for blood cancer, a bone marrow transplant can be the key for their survival.

One of the most compelling reasons to sign up as a bone marrow donor at the Day of Giving now in its 12th year is not only is it capable of saving a life, but the process of actually donating is fairly straightforward, no different than giving blood something the Day of Giving also offers onsite.

Jamie Spradlin, a 22-year-old teacher at Hobbs Elementary School in Cheyenne, learned that fact firsthand late last year, when she was called on to donate bone marrow.

It was at a Relay for Life event about four years ago, they had a booth and they were explaining, Would you like to save a life; do you want to know how? And I was with a group and all of us signed up, Spradlin said. It had to have been October or November of last year when they called me and said Hey, youre actually a match for someone.

Many people who register as potential bone marrow donors never get such a call. Thats because unlike blood, which falls into one of four types plus a positive or negative Rh factor, a bone marrow can be much harder to find. Only about 30 percent of patients looking for a bone marrow match can even find one in their own family the rest have to hope a stranger in the national donor registry happens to match them, according to the nonprofit Institute for Justice.

Only about 2 percent of Americans belong to the national bone marrow registry, and at least 3,000 people die each year because they cannot find a matching donor. The odds are worse for minorities, since bone marrow type is based partly on ethnic background while Caucasians can find an unrelated donor 75 percent of the time, the percentage drops to the 40s for Hispanic and Asian patients, and 25 percent for African Americans.

What happens if you do turn out to be a match for someone?

First they asked if I was still interested in donating, and I said yes, so then they had to wait on the person I was donating to to make sure it would all work out, Spradlin said.

In December 2016, she had to take a physical to ensure she was healthy enough to donate. Be The Match, the national bone marrow registry, paid all the expenses of her testing as well as travel.

They let me choose where I went for the physical, and my sister lives in Florida, so I went to do it there, Spradlin said. A few days after that they called and said everything was great, so then I went back down to Florida for the actual donation.

The donation process takes nearly a week of preparation. Twice a day, for five days, Spradlin said she went to a clinic to receive shots that caused her bones to produce more marrow stem cells.

The first day wasnt bad, but as I continued to get them every day thats when I started noticing my back and knees getting sore, she said. You know when you go to the gym and the next day your muscles are sore? Its just like that, but with your bones.

But that was the only real discomfort, she said, and given the stakes, it wasnt a tough call to keep going. For the donation itself, Spradlin underwent a process known as apheresis, where blood is removed from the body, the marrow stem cells are separated out, and blood is then returned.

Its kind of like donating blood. They had a needle in each of my arms, she said. One needle takes out the blood, a machine separates the stem cells from the blood and then the other needle puts the blood back in your arm.

Two months after the donation, Spradlin got an email from Be The Match informing her the recipient of her bone marrow was doing well Spradlins bone marrow had taken root, and the recipients body was regaining its ability to produce healthy blood cells.

Due to confidentiality concerns, Spradlin still doesnt know whose life she saved. It wont be until a year has passed that Be The Match offers to introduce donors to recipients.

All they told me was that she was a female, 41 years old and had some type of blood cancer, Spradlin said. But even knowing just that much, she added, I would absolutely do it again. It was an easy process to save someones life, and I think its crazy not many people sign up to become donors because its not a hard process.

I mean, I got to see my sister twice in Florida and they paid for everything, she added. Frankly, I felt lucky I got to be this persons donor.

How to help

This years community-wide Day of Giving will be from 8 a.m. to 5 p.m. Friday, May 12, at the Kiwanis Community House in Lions Park. A youth event will take place there the day before, May 11, from 3:30-6:30 p.m.

There are seven ways to help on the Day of Giving:

Day of Giving sorts and delivers all donations to local agencies.

For more information, visitCheyenneDayofGiving.org.

James Chilton is the Wyoming Tribune Eagles local government reporter. He can be reached atjchilton@wyomingnews.comor 307-633-3182. Follow him on Twitter at @JournoJChilton.

To go directly to the Wyoming Tribune Eagle's website, click here.

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Cheyenne's Day of Giving provides an opportunity to save a life - Wyoming Business Report

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When you think of tough athletes, football and hockey players quickly come to mind.

But a bowler?

Someone who learned that with determination and the love of family, friends, teammates and one anonymous bone marrow donor living 1,500 miles away striking down a rare and deadly blood disease is indeed possible?

Cameron Hurwitz stands 4-foot-11 and weighs 84 pounds with Skittles in his pockets.

But the Brighton (Rochester, N.Y.) High School freshman is a big man on the lanes, leading the Barons this season with a 216.5 average, making the coveted six-man state tournament composite team, where he led Section V to a third-place finish, and being named All-Greater Rochester for the second time in three seasons.

He has rolled three 300-games (two sanctioned) and just recently recorded a personal-best 799 series in competition.

There was a time when opponents sized up Hurwitz and took him for an easy mark. No more.

Hes pretty well-known now, Brighton coach Jason Wasserman said. What they cant believe is thathes only in ninth grade and doing as well as he is. He reads lane conditions as good as anyone out there. Hes able to make adjustments on the fly, he knows what equipment to use at what time and then hes just so consistent with his shots.

Thats what happens when you bowl nearly every day from the time youre eye level to a ball rack. When you have parents, Caryn and Scott Hurwitz, who nurture your gifts with unconditional love. When a big brother, Reese, a senior on the Brighton team with a fine 210 average of his own and is headed to Purdue to bowl, is always there to cheer the strikes and help you handle the splits and open frames of life.

Cameron, 14, a hard-throwing right-hander, throws a ball that takes a sharp, last-second right-to-left hook into the pocket that makes pins explode like fireworks on the Fourth of July.

He has had many mentors but in large part he is a self-taught prodigy.

As a big PBA fan who would like to compete on tour someday, he has long watched bowling on television and the internet. He reads bowling magazines, studies the history of the gameand can recite the career statistics of PBA stars. His favorite player is a kindred spirit, 5-foot-5 Norm Duke, a family friend whose autograph he wears proudly on his green Storm bowling shirt.

For good measure, Cameron drills his own balls, customizes his own bowling shoes (blue and fluorescent green on this day), and has ideas for other bowling products that his dad, who owns a motorcycle parts manufacturing business, helps bring to life. Some have already caught the attention of people in the industry.

I think it came from watching the pros on television all the time and picking it up, Cameron said when asked where his style and passion for all things bowling comes from. I love all the physics behind bowling and just the fact you have to use your mind to be able to perform. Anybody of any size can be great at bowling as long as you know the right way to do it and as long as you know what each piece of equipment does for a particular oil pattern.

Bowling alone during off-hours, wearing a mask to prevent against infection, Cameron Hurwitz never gave up on dream of normal life and returning to Brighton High School team.(Photo: CARYN HURWITZ)

Understanding bowling science helped Cameron enjoy his best season so far, but it was medical science that got him back on the lanes.

A little more than two years ago while in the seventh grade, Cameron was getting ready to leave for the Section V tournament when his mother spotted black-and-blue marks on his arms and legs. A phone call to their family doctor led to blood work, which led to instructions to take her son to the emergency room immediately.

He had extremely low platelets, which clot your blood, and they told us to pack a bag, youll be there for many days, Caryn Hurwitz said.

It was six days to be exact, during which Cameron was diagnosed with Aplastic Anemia, a rare and serious blood disorder in which the body stops making enoughnew white and red cells and platelets.

His bone marrow had just shut down and with so few platelets he was at great risk, and with no immunity he couldnt be around people, Caryn Hurwitz said.

While undergoing treatments at Golisano Childrens Hospital, Cameron was unable to attend school and was quarantined at home for over five months. When given the OK by doctors, his lone escape was making trips to area bowling centers where generous owners allowed him to practice during off-hours to the public.

Encouraged by upticks in his white cell counts, Camerons caregivers couldnt say no when he begged to compete in the prestigious United States Bowling Congress Junior Gold national championships in the Chicago area in July 2015. While wearing an antiviral mask and in between receiving seven-hour blood transfusions at a Chicago hospital, Cameron made the televised final, placing second in the U12 division.

The boy behind the mask became a media celebrity and inspiration in the bowling community. He made the cover of Bowlers Journal and PBA stars became his fans. Hall of Famer Pete Weber posted a good luck video message on Facebook to Cameron.

Hed bowl without hardly any oxygen (in his bloodstream), Caryn Hurwitz said. I dont think people really understood how hard it was for him, but as long as he could go, even with the low blood counts, he kept bowling. When I think about, Im amazed.

Unfortunately for Cameron, the treatments he received didnt produce the desired results and as his eighth-grade school year began, he was placed on the national Be the Matchbone marrow registry.

Waiting times for a match can vary, but in Camerons case one was found in just a few months. And on Dec. 29, 2015 he underwent a transplant at Boston Childrens Hospital, a painstaking procedure where a patients body is re-started with new stem cells that need time to grow and take hold.

Six weeks in the hospital were followed by six more months of isolation, school tutoring, the entire Hurwitz family living in the germ-free lane, and the family bonding like an alleys glued wooden strips.

Throughout his recovery, Cameron kept bowling after hours, determined to be ready for his freshman season. Bowling had become his medicine.

For the full story, visit the Rochester (N.Y.) Democrat and Chronicle

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N.Y. bowler rolls on following bone marrow transplant - USA TODAY High School Sports

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NEW YORK--(BUSINESS WIRE)--

DKMS, the international non-profit leading the fight against blood cancer, teamed with the film industry and launched #CastingforaHero, a campaign designed to raise awareness about diversity in bone marrow donation and to urge more people to swab their cheeks and register as potential lifesaving bone marrow/blood stem cell donors. The campaign was first launched by actor/producer Vin Diesel, has been supported on social media by Fast franchise players Tyrese Gibson, Cris Bridges (Ludacris), Don Omar and the brother of late actor Paul Walker, Cody Walker, and will be joined by other cast members to support the campaign this month. It has also garnered support by a number of celebrities including Guardians of the Galaxy actress, Zoe Saldana and Larenz Tate. Tate appeared on the television show POWER, alongside Charlie Murphy, who passed away earlier this month from complications related to blood cancer.

This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20170417005737/en/

Diesel launched the campaign on his Instagram (@vindiesel) posting, Today, premiere day (April 8), I am proud to launch#CastingforaHero- a campaign to save lives by increasing the multicultural community's presence in the worldwide bone marrow registries.

The campaign was conceived by DKMS through a partnership with Samantha Vincent, (Executive Producer, the Fate of the Furious) and Frank E. Flowers (Director, Haven) after they lost a family member to leukemia and became aware of the overwhelming odds faced by minorities and those of mixed race backgrounds of finding an unrelated match due to being underrepresented on the registry. Of all donors registered only 6% are African American, 9% are Hispanic/Latino, 6% are Asians, and 4% are Mixed Race.

In partnership with the community, one of the nations premier cross cultural creative advertising agencies, the #castingforahero concept was developed and executed through social and experiential channels leveraging key influencers with the goal of raising awareness and activating younger donors. The campaign was launched with the support of Universal Pictures, Saturday, April 8 during the Fate of the Furious #F8 premiere at Radio City Music Hall in NYC, with #castingforahero photo booths present at the F8premiere after party which gave VIP guests an opportunity to register.

In the companion video, written and directed by Flowers and produced by Andrew Molina, Anne McCarthy (Casting Director, Furious 7) and her associates audition real-life unknown actors for a hero role where they are asked to cold-read scripts about the lack of diversity on the bone marrow registry. The actors become emotional upon learning the scripts are in fact about themselves and their own chances to beat a disease like leukemia if there are not enough potential donors registered who share the same ancestry. The video calls for more trueheroes potential bone marrow/blood stem cell donors to join the effort to fight blood cancer and help find more matches for people of all ethnic backgrounds.

The newly launched website, castingforahero.com, allows people to create their own casting photo with custom skins representing unique identities and share on their social media platforms, while directing them to register with DKMS as a potential lifesaving donor.

Each year thousands of people lose the fight against blood cancer because they are unable to find their hero: a lifesaving bone marrow match, said Katharina Harf, co-founder of DKMS US. #CastingforaHero will help bring attention to the need for more diversity among potential bone marrow donors. By registering to become a DKMS donor, you can change the odds and become a life-saving hero yourself.

For more information about #CastingforaHero, visit http://www.castingforahero.com. To learn more about DKMS or register as a potential lifesaving donor, please visit http://www.dkms.org/register or @dkms.us.

About DKMS

DKMS is an international nonprofit organization dedicated to eradicating blood cancers like Leukemia and other blood-related illnesses inspiring both men and women around the world to register as bone marrow and blood stem cell donors. DKMS is providing patients with a second chance at life, working closely with families from diagnosis to transplant and beyond. The donor journey begins with a swab of the cheek that takes less than 60 seconds and can be the action that leads to a lifesaving transplant. DKMS, originally founded in Germany in 1991 by Dr. Peter Harf, has organizations in Poland, Spain, the United Kingdom and the United States. The U.S. office was started in 2004. Globally, DKMS has registered more than 7.2 million people. To join the fight against blood cancer or for more information, please go to dkms.org or @DKMS.us.

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DKMS Creates Celebrity Driven #Castingforahero Campaign - Yahoo Finance

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BY: DUSTIN BATTY

Stem cell research is a controversial topic that is often vilified in the minds of the general public. This is in part because of the vast mainstream media coverage of the debates surrounding the use of embryonic stem cells, and their tendency to refer to the issue simply as the stem cell controversy rather than specifying that the problematic stem cells are those harvested from embryos.

Embryonic stem cells aside, though, there is still some discussion in bioethical circles about the harvesting of stem cells from bone marrow and even from skin. According to a study exploring an alternative method of obtaining stem cells, the debates surrounding the extraction of stem cells from even a mildly invasive procedure such as a skin biopsy are particularly relevant when one is procuring cells from vulnerable populations, such as children and individuals with intellectual disability. The study was undertaken to prove the viability of a non-invasive method of procuring stem cells from individuals with Down syndrome.

The method used by the researchers was surprisingly successful. They managed to extract cells from urine samples that were able to become induced pluripotent stem cells (iPSC), which means that the cells were altered so they could act like stem cells. Notably, the iPSCs obtained from the urine samples were superior to those harvested from skin biopsies and other methods because theyd had no exposure to ultraviolet light, and thus their DNA was generally undamaged.

Perhaps the most significant advantage that iPSCs from urine samples have over other methods is their completely non-invasive nature. This is particularly true when collecting stem cells from individuals with Down syndrome; in the past, a significant percentage of such individuals or their parents or guardians have refused to go forward with skin biopsies, limiting the availability of material for developing treatment methods. Research ethics boards have also been known to prevent the wide-scale use of skin biopsies in individuals with DS [Down syndrome]. This new method is expected to relieve the anxieties of the individuals involved, and should be easily accepted by ethics boards as well.

The researchers expect that the use of this method will improve both the quality of cells used and the quantity available to be studied. This increased availability is important to the efficient continuation of research into treatments for Down syndrome. Although such research begins with the use of lab mice to test the viability of new treatment methods, mouse physiology is so much simpler than that of humans that such tests arent sufficient. Eventually, the treatment needs to be tested on human cells. Stem cells are particularly useful for these kinds of tests because they are able to grow into a variety of different cells, which can be tested with the treatment individually.

The researchers conclude with the assurance that the techniques they implemented could be useful not only for research into Down syndrome, but also in the study of other neurodevelopmental and neurodegenerative disorders.

Providing better quality cells with increased participation and no ethical concerns, this new method of harvesting stem cells could be the answer that medical researchers were looking for.

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Stem cells can now be gathered from urine samples - The Plaid Zebra (blog)

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Scientists have created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack, researchers at University of Minnesota in the US said. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die.

Our bodies can not replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure. Researchers used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries. This is a significant step forward in treating the No 1 cause of death in the US, said Brenda Ogle, an associate professor at the University of Minnesota.

We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years, said Ogle. Ogle said that the research is different from previous ones as the patch is modelled after a digital, three- dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.

Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue, researchers said. We were quite surprised by how well it worked given the complexity of the heart. We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch, Ogle said.

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart. The study was published in the journal Circulation Research.

Publish date: April 16, 2017 12:57 pm| Modified date: April 16, 2017 12:57 pm

Tags: 3D-Bioprint, Brenda Ogle, cells, Heart, heart attack, heart failure, Journal Circulation Research, scientists, structural proteins, University of Minnesota

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Scientists have made a 3D-printed patch that can help heal the damaged heart tissue - Tech2 (blog)

Cardiac Stem Cells Comments Off on Scientists have made a 3D-printed patch that can help heal the damaged heart tissue – Tech2 (blog) | April 16th, 2017

April 11, 2017 07:15 ET | Source: Cesca Therapeutics Inc.

RANCHO CORDOVA, Calif., April 11, 2017 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (Nasdaq:KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Dr. Xiaochun (Chris) Xu, Chairman and Interim Chief Executive Officer and Chairman of Boyalife Group, will present an overview of the Companys cardiovascular clinical research program at the 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair, being held April 10-12, 2017 at the Hope Hotel in Shanghai, China.

Details of the presentation are as follows:

Despite recent therapeutic and surgical advances, the effects of peripheral arterial disease, including heart attack and critical limb ischemia (CLI), remain among the worlds leading causes of morbidity and mortality and represent a rapidly escalating public health crisis, noted Dr. Xu. I look forward to presenting a review of our latest findings, including key feasibility study results and an overview of our Phase 3 Critical Limb Ischemia Rapid Stemcell Treatment (CLIRST) trial, which we believe highlight the potential of Cesca Therapeutics proprietary AutoXpress point-of-care platform to deliver autologous cell-based therapies that may represent a new paradigm in patient treatment going forward.

About the Symposium of Translational Medicine in Stem Cell Myocardial Repair

The 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair brings together more than 650 of the worlds cardiac disease thought leaders to discuss the potential of translational and regenerative medicine in treating myocardial infarction (MI) and cardiac failure. The symposium is co-sponsored by the Shanghai Society for Cell Biology, the Institute of Health Sciences, the Shanghai Cardiovascular Disease Institute, the Guangzhou Institutes of Biomedicine and Health, and the Key Laboratory of Stem Cell Biology, Shanghai.

About Cesca Therapeutics Inc.

Cesca is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. Cesca is an affiliate of the Boyalife Group (http://www.boyalifegroup.com), a China-based industrial-research alliance among top research institutes for stem cell and regenerative medicine.

Forward-Looking Statement

The statements contained herein may include statements of future expectations and other forward-looking statements that are based on managements current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

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CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell ... - GlobeNewswire (press release)

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Joseph Baucum , jbaucum@pnj.com Published 4:06 p.m. CT April 16, 2017 | Updated 26 minutes ago

Andrews Institute is conducting new stem cell research that could impact the FDA approval of certain treatments. Joseph Baucumjbaucum@pnj.com

Dr. Andrew Anz, an orthopedic surgeon and sports medicine specialist at the Andrews Institute in Gulf Breeze is working on cutting-edge stem cell research for cartilage therapy.(Photo: Tony Giberson/tgiberson@pnj.com)Buy Photo

By the time most reach age 55, Adam Anz estimatesas much as 30 percent of the population will incur some form of knee degeneration, a problem that equals pain and in many cases, surgery.

Its a problem that were all going to face at some point in our lives, said Anz, orthopaedic surgeon at Andrews Institute for Orthopaedics & Sports Medicine.

But in May, a new study will begin at Andrews Institute in Gulf Breeze that could play a game-changing role in evolving the range of medicine available for treating knee injuries. In the process, the research may also help drive down patients costs.

Anz will help spearhead a study next month into increasing the amount of stem cells doctors are able to harvest from bone marrow transplants with the goal of utilizing those cells to regrow cartilage in knees. Cartilage, a tough and flexible material, is essential to the knee, because it acts as a cushion between the bones in the joint. Damaged cartilage can often necessitate knee replacement.

ADDITIONAL CONTENT:Andrews Institute expands prep athletics care in region

In the study, Anz said researchers will attempt to increase the amount of stem cells in participants bone marrow, which would then empty from the marrow into their bloodstream. Researchers would collect the blood, separate the stem cells from it and inject the cells into patients knees. Doctors would then monitor if the marrow cells transform into cartilage cells and spark regeneration.

Its about determining how can we obtain those cells in efficient quantities and put those cells in the right place at the right time to help with healing patients injuries, Anz said.

Because the Food & Drug Administration has not approved the vast majority of stem cell-based remedies, not all treatments involving the cells are available for patients, including the cartilage procedure. For the treatments that are offered, health insurance providers do not cover them without the FDAs consent. Patients who choose to undergo them must pay out-of-pocket prices.

The study at Andrews Institute could push a stem cell cartilage treatment closer to FDA approval and by extension, availability and affordability. The research is an official FDA study. It is led by Khay Yong Saw, a Malaysian physicianwho has already demonstrated conceptual proof of the treatment in an animal study in 2006. He completed a randomized control trial in 2012. This study is the next step in proving the safety and efficacy of the procedure to gain federal endorsement.

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ADDITIONAL CONTENT:Elite athletes just piece of Andrews Institute

Anz, optimistic about the studys potential, emphasized more research must be conducted into the effectiveness of stem cell treatments those already available and those still in the testing phase.

Its important to be excited about technologies, but its also important to be honest with the patients that more must be done to show these treatments are effective, said Anz, who estimated the cartilage study to require two years for participant enrollment and another two years before researchers can observe outcomes.

But some who have undergone stem cell treatments advocate for the procedures federal approval. Jody Falvey, a retired Pensacola resident, had a stem cell procedure conducted at Andrews Institute on her knee in the fall of 2012.

Falvey, 67, tore the medial and lateral meniscus in her knee during a family visit to South Florida while brewing coffee in the morning. The sensation, she said, felt like a knife slicing through her joint.

Following a consultation with Anz, who described an available stem cell treatment known as bone marrow aspirate concentrate, Falvey chose to have the procedure done. The treatment utilized cells from her own body to repair the knee. The process, from procedure to recovery, spanned about two years.

Falvey said her knee does not feel like it ever underwent surgery. The fact that it helped prevent her from having to undergo a knee replacement made the operation even better.

I did not want metal in my body, she said. This was just one of the greatest alternatives I had heard of. I would do it again in a heartbeat.

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Andrews Institute expands prep athletics care in region

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Andrews Institute to study stem cells' impact on knee - Pensacola News Journal

Bone Marrow Stem Cells Comments Off on Andrews Institute to study stem cells’ impact on knee – Pensacola News Journal | April 16th, 2017

Stem cells have been touted as treatments for everything from hair loss to heart disease.

But are those claims scientifically sound?

Research on the technology continues to look promising, but many of its human applications are still preliminary and their effectiveness anecdotal.

Samumed, a $12 billion biotech start-up based in San Diego, profiled this month in Business Insider, exemplifies both sides of the coin.

The company has promised a bevy of age-reversing cures, including regrowing hair, treating wrinkles, and regenerating cartilage in people with osteoarthritis

However, their research isnt conclusive.

None of their treatments have received government approval yet.

Read more: Rheumatoid arthritis and stem cell treatments

Its easy to get excited about all this research.

Samumed Is Trying to Create the Fountain of Youth, says one headline.

Samumed Aims to Reverse Aging with Eternal Youth Treatments, says another.

Combined with $300 million in investment funding, the company has more than just buzz going for it in the biotech industry.

Their treatment for androgenetic alopecia (hair loss) is currently in phase II trials.

Its program to help people with osteoarthritis regrow cartilage in their knees is in phase III.

In total, the company has seven drugs in phase II trials, with plans to expand into more areas of disease research this year.

However, Samumed has raised some eyebrows in the industry with its secrecy. Some skeptics have likened the company to Theranos, a biotech start-up that was valued at $9 billion before an investigation by the Wall Street Journal led to a shutdown of the companys labs.

Samumed has been more open about presenting their data to the public but not about the actual treatments.

We're basically telling everyone, here's proof that it works, Samumed Chief Executive Officer, Osman Kibar, told Business Insider. How it works you just need to wait a little longer because we want to build as much of a head start as we can.

Read more: Stem cell treatments for multiple sclerosis

Beyond the applications of stem cells at Samumed, the technology is also being used to treat some of the United States most widespread health issues.

New research from the American Heart Association this month demonstrated the effectiveness of implanted stem cells into the hearts of people with cardiomyopathy.

Although the sample size was small (only 27 people), scientists noted function and symptomatic improvements of heart functioning as well as less frequency of hospitalization and lower medical costs. They conclude that the stem cell procedure is a feasible treatment for cardiomyopathy, but they note that a larger clinical follow-up is needed for more conclusive results.

In the past week, Newsweek reported on miracle stem cell treatments for burn victims that will promote healing without scars.

Stat News wrote about research on stem cells in mice that could potentially help cure Parkinsons disease.

Read more: Unproved stem cell treatments offer hope and risk

Some researchers in the industry are somewhat measured in their optimism of the technologys human applications.

I want to make sure that we provide a real cautionary note, especially to those individuals and those institutions that tout stem cells as the panacea for any ill, Dr. Cato Laurencin, director of the Institute for Regenerative Engineering at the University of Connecticut, told Healthline.

Laurencin, a medical practitioner at the forefront of stem cell technology, is a firm believer in the benefits of the treatment, but also remains skeptical of some of the claims associated with it.

Much of the evidence is still preliminary or anecdotal, and when people operate on information that is preliminary or anecdotal, there is the possibility for harm, he said.

His work in regenerative engineering a term he coined several years ago looks at the healing properties of implanted stem cells in the human body.

In research published this month, Laurencin and his team concluded that stem cells effectively improved healing to torn rotator cuff tendons in rats.

Rotator cuff tendon tears are a relatively common injury in humans and can be difficult to treat.

Unlike other tendons in the body, the rotator cuff tendon is unable to heal itself, said Laurencin.

Once it is torn, it is liable to be reinjured again and again.

However, the research released this month is about more than just applying stem cells to a certain kind of injury, its about how the stem cells are applied.

Read more: Scientists use 3-D environment to speed up growth of stem cells

Laurencin describes his field as an evolution of earlier work from 30 years ago in tissue engineering: a convergence of bringing together new technologies to create new science and new possibilities.

In this case, nanotechnology is at the heart of this stem cell operation.

Currently there are a variety of ways that stem cells can be implanted into a subject, including injections and bone marrow transplants.

For his research, Laurencin and his team used biomaterial based fiber matrices a nanomaterial conducive to growing and attaching stem cells to implant into the wounded area.

The results are promising, but Laurencin and his team will have to continue working with animals for some time before the process can be applied to humans.

The key is in understanding that stem cells have the potential for more than just regrowing damaged parts of the body.

The way we commonly think about a stem cell is it becoming a new tissue. But were also understanding that the stem cell itself can secrete biological factors that help regeneration occur. Thats what we think is happening here, said Laurencin.

His research into stem cells as a medicinal element in the body could have far reaching implications for all kinds of wound therapy.

Despite his measured approach, Laurencin is still willing to hypothesize about the excitement that the future of the field undoubtedly holds with proper time, funding, and research.

There are newts and salamanders that can regenerate a limb, he told Healthline.

How do we harness the cues that are taking place in these types of animals, and can we utilize what weve learned from these types of animals in humans?

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Stem Cell Research Advancing Rapidly - Healthline

Bone Marrow Stem Cells Comments Off on Stem Cell Research Advancing Rapidly – Healthline | April 16th, 2017

Stem cells are a rapidly advancing field of biological research. Since Dr. James Thomson first cultivated human embryonic stem cells at the University of Wisconsin - Madison in the late 1990s, this field of researched has exploded with potential. The links below provide access to a curriculum developed under the supervision of Dr. Thomson as well as the co-directors and staff of the UW Stem Cell & Regenerative Medicine Center. The material has been reviewed for accuracy by the scientists actually conducting the research and was compiled and formatted by Craig Kohn, a high school teacher with research experience, for a high school audience. The PowerPoint presentation works in conjunction with the notesheet, allowing for students to work independently if preferred. More information about specific instructional practices can be found below in Teacher Notes. PowerPoint: http://bit.ly/ted-stemcells Notesheet: http://bit.ly/ted-stemcellsnotesheet Quiz: http://bit.ly/ted-stemcellsquiz Additional resources about stem cells can be found at: http://www.stemcells.wisc.edu/node/386 http://stemcells.nih.gov/Pages/Default.aspxhttp://www.stemcellschool.org/http://www.nursingdegree.net/blog/750/25-best-blogs-for-following-stem-cell-research/

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What are stem cells? - Craig A. Kohn | TED-Ed

Skin Stem Cells Comments Off on What are stem cells? – Craig A. Kohn | TED-Ed | April 16th, 2017

Salk Institute and Chinese researchers report creating a new kind of stem cell, one that is more versatile than any other normally grown in the lab.

Called an extended pluripotent stem cell, it can give rise to every cell type in the body, the researchers say in a recent study. This includes the extra-embryonic tissues such as the placenta that support the developing baby. Just one cell can generate a complete organism.

Embryonic stem cells and artificial embryonic stem cells called induced pluripotent stem cells cant make these extra-embryonic tissues. So neither embryonic nor IPS cells can give rise to a complete embryo, because the supportive tissues necessary for an embryo to survive arent there.

But the extended pluripotent stem cells can reliably give rise to both types of cells, and thus whole embryos and offspring, the scientists report.

The EPS cells were made from human and mouse embryonic stem cells. In addition, they were produced from skin cells, or fibroblasts by treating them with a chemical cocktail. IPS cells, invented in 2006, are generated from fibroblasts by a similar reprogramming process.

Use of IPS cells is regarded as morally acceptable by those who oppose use of human embryonic stem cells, because they cant form an entire embryo. This is the reasoning of the Catholic Church. But since the EPS cells can make whole embryos, at least in mice, how the church will react is unclear.

To demonstrate this ability to make all cell types, the researchers grew an entire mouse from just one EPS cell. They also grew chimeric mice, with human EPS cells integrating into the mice better than embryonic stem cells did.

The study on these new stem cells was published April 6 in the journal Cell. It can be found at j.mp/extendedstem.

Better tool

That characteristic of creating every cell in the body, called totipotency, is normally found only at the very beginning of embryonic development. Embryonic stem cells are usually extracted too late, when the cells have already divided into the embryonic and extra-embryonic lineages.

Totipotent stem cells have been observed in the lab, but they lasted briefly, and didnt yield stable totipotent cell lines.

Salk Institute stem cell researcher Juan Carlos Izpisa Bemonte was a cosenior author of the paper along with Hongkui Deng of Peking University in Beijing. The first authors were Yang Yang, Bei Liu, Jun Xu, and Jinlin Wang; all of Peking University, and Jun Wu, of the Salk Institute.

EPS cell lines provide a useful cellular tool for gaining a better molecular understanding of initial cell fate commitments and generating new animal models to investigate basic questions concerning development of the placenta, yolk sac, and embryo proper, the study stated.

Furthermore, they also provide an unlimited cell resource and hold great potential for in vivo disease modeling, in vivo drug discovery, and in vivo tissue generation in the future. Finally, our study opens a path toward capturing stem cells with intra- and/or inter-species bi-potent chimeric competency from a variety of other mammalian species.

Organs for transplant

The creation of chimeric mice is part of Izpisa Bemontes longstanding goal of growing human organs in animals for transplant.

While mice are too small to grow organs for transplant, they serve as a model to understand how cells from a different species, can be grown in a host body. In this new study, the mice served as a model of how well the EPS cells can integrate.

Izpisa Bemonte is now working to translate his research on chimeric mice to pigs, which are large enough to provide human organs. In January, a team he led reported on work with human-pig chimeras, which were not allowed to grow past the embryonic stage. They also created rat-mice chimeras.

The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs, Wu said in a Salk statement. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.

We believe that the derivation of a stable stem cell line with totipotent-like features will have a broad and resounding impact on the stem cell field, Izpisua Belmonte said in the statement.

The work was funded by a number of sources. They include: the National Key Research and Development Program of China; the National Natural Science Foundation of China; the Guangdong Innovative and Entrepreneurial Research Team Program; the Science and Technology Planning Project of Guangdong Province, China; the Science and Technology Program of Guangzhou, China; the Ministry of Education of China (111 Project); the BeiHao Stem Cell and Q9 Regenerative Medicine Translational Research Institute; the Joint Institute of Peking University Health Science Center; University of Michigan Health System; Peking-Tsinghua Center for Life Sciences; the National Science and Technology Support Project; the CAS Key Technology Talent Program; the G. Harold and Leila Y. Mathers Charitable Foundation; and The Moxie Foundation.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Stem cell invented that can grow into any tissue in the body - The ... - The San Diego Union-Tribune

Skin Stem Cells Comments Off on Stem cell invented that can grow into any tissue in the body – The … – The San Diego Union-Tribune | April 16th, 2017

TERT Identifiers Aliases TERT, CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT, hEST2, hTRT, telomerase reverse transcriptase External IDs OMIM: 187270 MGI: 1202709 HomoloGene: 31141 GeneCards: TERT Genetically Related Diseases breast cancer, interstitial lung disease, adenocarcinoma of the lung, prostate cancer, se atraganto con un caramelo, testicular germ cell cancer, idiopathic pulmonary fibrosis, malignant glioma[1] RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 5: 1.25 1.3 Mb Chr 13: 73.63 73.65 Mb PubMed search [2] [3] Wikidata View/Edit Human View/Edit Mouse

Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.[4][5]

Telomerases are part of a distinct subgroup of RNA-dependent polymerases. Telomerase lengthens telomeres in DNA strands, thereby allowing senescent cells that would otherwise become postmitotic and undergo apoptosis to exceed the Hayflick limit and become potentially immortal, as is often the case with cancerous cells. To be specific, TERT is responsible for catalyzing the addition of nucleotides in a TTAGGG sequence to the ends of a chromosomes telomeres.[6] This addition of repetitive DNA sequences prevents degradation of the chromosomal ends following multiple rounds of replication.[7]

hTERT absence (usually as a result of a chromosomal mutation) is associated with the disorder Cri du chat.[8][9]

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity.[10]

The hTERT gene, located on chromosome 5, consists of 16 exons and 15 introns spanning 35 kb. The core promoter of hTERT includes 330 base pairs upstream of the translation start site (AUG since it's RNA by using the words "exons" and "introns"), as well as 37 base pairs of exon 2 of the hTERT gene.[11][12][13] The hTERT promoter is GC-rich and lacks TATA and CAAT boxes but contains many sites for several transcription factors giving indication of a high level of regulation by multiple factors in many cellular contexts.[11] Transcription factors that can activate hTERT include many oncogenes (cancer-causing genes) such as c-Myc, Sp1, HIF-1, AP2, and many more, while many cancer suppressing genes such as p53, WT1, and Menin produce factors that suppress hTERT activity .[13][14] Another form of up-regulation is through demethylation of histones proximal to the promoter region, imitating the low density of trimethylated histones seen in embryonic stem cells.[15] This allows for the recruitment of histone acetyltransferase (HAT) to unwind the sequence allowing for transcription of the gene.[14]

Telomere deficiency is often linked to aging, cancers and the conditions dyskeratosis congenita (DKC) and Cri du chat. Meanwhile, over-expression of hTERT is often associated with cancers and tumor formation.[8][16][17][18] The regulation of hTERT is extremely important to the maintenance of stem and cancer cells and can be used in multiple ways in the field of regenerative medicine.

hTERT is often up-regulated in cells that divide rapidly, including both embryonic stem cells and adult stem cells.[17] It elongates the telomeres of stem cells, which, as a consequence, increases the lifespan of the stem cells by allowing for indefinite division without shortening of telomeres. Therefore, it is responsible for the self-renewal properties of stem cells. Telomerase are found specifically to target shorter telomere over longer telomere, due to various regulatory mechanisms inside the cells that reduce the affinity of telomerase to longer telomeres. This preferential affinity maintains a balance within the cell such that the telomeres are of sufficient length for their function and yet, at the same time, not contribute to aberrant telomere elongation [19]

High expression of hTERT is also often used as a landmark for pluripotency and multipotency state of embryonic and adult stem cells. Over-expression of hTERT was found to immortalize certain cell types as well as impart different interesting properties to different stem cells.[13][20]

hTERT immortalizes various normal cells in culture, thereby endowing the self-renewal properties of stem cells to non-stem cell cultures.[13][21] There are multiple ways in which immortalization of non-stem cells can be achieved, one of which being via the introduction of hTERT into the cells. Differentiated cells often express hTERC and TP1, a telomerase-associated protein that helps form the telomerase assembly, but does not express hTERT. Hence, hTERT acts as the limiting factor for telomerase activity in differentiated cells [13][22] However, with hTERT over-expression, active telomerase can be formed in differentiated cells. This method has been used to immortalize prostate epithelial and stromal-derived cells, which are typically difficult to culture in vitro. hTERT introduction allows in vitro culture of these cells and available for possible future research. hTERT introduction have an advantage over the use of viral protein for immortalization in that it does not involve the inactivation of tumor suppressor gene, which might lead to cancer formation.[21]

Over-expression of hTERT in stem cells changes the properties of the cells.[20][23][24] hTERT over-expression increases the stem cell properties of human mesenchymal stem cells. The expression profile of mesenchymal stem cells converges towards embryonic stem cells, suggesting that these cells may have embryonic stem cell-like properties. However, it has been observed that mesenchymal stem cells undergo decreased levels of spontaneous differentiation.[20] This suggests that the differentiation capacity of adult stem cells may be dependent on telomerase activities. Therefore, over-expression of hTERT, which is akin to increasing telomerase activities, may create adult stem cells with a larger capacity for differentiation and hence, a larger capacity for treatment.

Increasing the telomerase activities in stem cells gives different effects depending on the intrinsic nature of the different types of stem cells.[17] Hence, not all stem cells will have increased stem-cell properties. For example, research has shown that telomerase can be upregulated in CD34+ Umbilical Cord Blood Cells through hTERT over-expression. The survival of these stem cells was enhanced, although there was no increase in the amount of population doubling.[24]

Deregulation of telomerase expression in somatic cells may be involved in oncogenesis.[10]

Genome-wide association studies suggest TERT is a susceptibility gene for development of many cancers,[25] including lung cancer.[26]

Telomerase activity is associated with the number of times a cell can divide playing an important role in the immortality of cell lines, such as cancer cells. The enzyme complex acts through the addition of telomeric repeats to the ends of chromosomal DNA. This generates immortal cancer cells.[27] In fact, there is a strong correlation between telomerase activity and malignant tumors or cancerous cell lines.[28] Not all types of human cancer have increased telomerase activity. 90% of cancers are characterized by increased telomerase activity.[28]Lung cancer is the most well characterized type of cancer associated with telomerase.[29] There is a lack of substantial telomerase activity in some cell types such as primary human fibroblasts, which become senescent after about 3050 population doublings.[28] There is also evidence that telomerase activity is increased in tissues, such as germ cell lines, that are self-renewing. Normal somatic cells, on the other hand, do not have detectable telomerase activity.[30] Since the catalytic component of telomerase is its reverse transcriptase, hTERT, and the RNA component hTERC, hTERT is an important gene to investigate in terms of cancer and tumorigenesis.

The hTERT gene has been examined for mutations and their association with the risk of contracting cancer. Over two hundred combinations of hTERT polymorphisms and cancer development have been found.[29] There were several different types of cancer involved, and the strength of the correlation between the polymorphism and developing cancer varied from weak to strong.[29] The regulation of hTERT has also been researched to determine possible mechanisms of telomerase activation in cancer cells. Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells.[27] GSK3 is involved in promoter activation through controlling a network of transcription factors.[27]Leptin is also involved in increasing mRNA expression of hTERT via signal transducer and activation of transcription 3 (STAT3), proposing a mechanism for increased cancer incidence in obese individuals.[27] There are several other regulatory mechanisms that are altered or aberrant in cancer cells, including the Ras signaling pathway and other transcriptional regulators.[27]Phosphorylation is also a key process of post-transcriptional modification that regulates mRNA expression and cellular localization.[27] Clearly, there are many regulatory mechanisms of activation and repression of hTERT and telomerase activity in the cell, providing methods of immortalization in cancer cells.

If increased telomerase activity is associated with malignancy, then possible cancer treatments could involve inhibiting its catalytic component, hTERT, to reduce the enzymes activity and cause cell death. Since normal somatic cells do not express TERT, telomerase inhibition in cancer cells can cause senescence and apoptosis without affecting normal human cells.[27] It has been found that dominant-negative mutants of hTERT could reduce telomerase activity within the cell.[28] This led to apoptosis and cell death in cells with short telomere lengths, a promising result for cancer treatment.[28] Although cells with long telomeres did not experience apoptosis, they developed mortal characteristics and underwent telomere shortening.[28] Telomerase activity has also been found to be inhibited by phytochemicals such as isoprenoids, genistein, curcumin, etc.[27] These chemicals play a role in inhibiting the mTOR pathway via down-regulation of phosphorylation.[27] The mTOR pathway is very important in regulating protein synthesis and it interacts with telomerase to increase its expression.[27] Several other chemicals have been found to inhibit telomerase activity and are currently being tested as potential clinical treatment options such as nucleoside analogues, retinoic acid derivatives, quinolone antibiotics, and catechin derivatives.[30] There are also other molecular genetic-based methods of inhibiting telomerase, such as antisense therapy and RNA interference.[30]

hTERT peptide fragments have been shown to induce a cytotoxic T-cell reaction against telomerase-positive tumor cells in vitro.[31] The response is mediated by dendritic cells, which can display hTERT-associated antigens on MHC class I and II receptors following adenoviral transduction of an hTERT plasmid into dendritic cells, which mediate T-cell responses.[32] Dendritic cells are then able to present telomerase-associated antigens even with undetectable amounts of telomerase activity, as long as the hTERT plasmid is present.[33]Immunotherapy against telomerase-positive tumor cells is a promising field in cancer research that has been shown to be effective in in vitro and mouse model studies.[34]

Induced pluripotent stem cells (iPS cells) are somatic cells that have been reprogrammed into a stem cell-like state by the introduction of four factors (Oct3/4, Sox2, Klf4, and c-Myc).[35] iPS cells have the ability to self-renew indefinitely and contribute to all three germ layers when implanted into a blastocyst or use in teratoma formation.[35]

Early development of iPS cell lines were not efficient, as they yielded up to 5% of somatic cells successfully reprogrammed into a stem cell-like state.[36] By using immortalized somatic cells (differentiated cells with hTERT upregulated), iPS cell reprogramming was increased by twentyfold compared to reprogramming using mortal cells.[36]

The reactivation of hTERT, and subsequently telomerase, in human iPS cells has been used as an indication of pluripotency and reprogramming to an ES (embryonic stem) cell-like state when using mortal cells.[35] Reprogrammed cells that do not express sufficient hTERT levels enter a quiescent state following a number of replications depending on the length of the telomeres while maintaining stem cell-like abilities to differentiate.[36] Reactivation of TERT activity can be achieved using only three of the four reprogramming factors described by Takahashi and Yamanaka: To be specific, Oct3/4, Sox2 and Klf4 are essential, whereas c-Myc is not.[15] However, this study was done with cells containing endogenous levels of c-Myc that may have been sufficient for reprogramming.

Telomere length in healthy adult cells elongates and acquires epigenetic characteristics similar to those of ES cells when reprogrammed as iPS cells. Some epigenetic characteristics of ES cells include a low density of tri-methylated histones H3K9 and H4K20 at telomeres, as well as an increased detectable amount of TERT transcripts and protein activity.[15] Without the restoration of TERT and associated telomerase proteins, the efficiency of iPS cells would be drastically reduced. iPS cells would also lose the ability to self-renew and would eventually senesce.[15]

DKC (dyskeratosis congenita) patients are all characterized by the defective maintenance of telomeres leading to problems with stem cell regeneration.[16] iPS cells derived from DKC patients with a heterozygous mutation on the TERT gene display a 50% reduction in telomerase activity compared to wild type iPS cells.[37] Conversely, mutations on the TERC gene (RNA portion of telomerase complex) can be overcome by up-regulation due to reprogramming as long as the hTERT gene is intact and functional.[38] Lastly, iPS cells generated with DKC cells with a mutated dyskerin (DKC1) gene cannot assemble the hTERT/RNA complex and thus do not have functional telomerase.[37]

The functionality and efficiency of a reprogrammed iPS cell is determined by the ability of the cell to re-activate the telomerase complex and elongate its telomeres allowing for self-renewal. hTERT is a major limiting component of the telomerase complex and a deficiency of intact hTERT impedes the activity of telomerase, making iPS cells an unsuitable pathway towards therapy for telomere-deficient disorders.[37]

Although the mechanism is not fully understood, exposure of TERT-deficient hematopoietic cells to androgens resulted in an increased level of TERT activity.[39] Cells with a heterozygous TERT mutation, like those in DKC (dyskeratosis congenita) patients, which normally exhibit low baseline levels of TERT, could be restored to normal levels comparable to control cells. TERT mRNA levels are also increased with exposure to androgens.[39] Androgen therapy may become a suitable method for treating circulatory ailments such as bone marrow degeneration and low blood count linked with DKC and other telomerase-deficient conditions.[39]

As organisms age and cells proliferate, telomeres shorten with each round of replication. Cells restricted to a specific lineage are capable of division only a set number of times, set by the length of telomeres, before they senesce.[40] Depletion and uncapping of telomeres has been linked to organ degeneration, failure, and fibrosis due to progenitors' becoming quiescent and unable to differentiate.[19][40] Using an in vivo TERT deficient mouse model, reactivation of the TERT gene in quiescent populations in multiple organs reactivated telomerase and restored the cells abilities to differentiate.[41] Reactivation of TERT down-regulates DNA damage signals associated with cellular mitotic checkpoints allowing for proliferation and elimination of a degenerative phenotype.[41] In another study, introducing the TERT gene into healthy one-year-old mice using an engineered adeno-associated virus led to a 24% increase in lifespan, without any increase in cancer.[42]

The hTERT gene has become a main focus for gene therapy involving cancer due to its expression in tumor cells but not somatic adult cells.[43] One method is to prevent the translation of hTERT mRNA through the introduction of siRNA, which are complimentary sequences that bind to the mRNA preventing processing of the gene post transcription.[44] This method does not completely eliminate telomerase activity, but it does lower telomerase activity and levels of hTERT mRNA seen in the cytoplasm.[44] Higher success rates were seen in vitro when combining the use of antisense hTERT sequences with the introduction of a tumor-suppressing plasmid by adenovirus infection such as PTEN.[45]

Another method that has been studied is manipulating the hTERT promoter to induce apoptosis in tumor cells. Plasmid DNA sequences can be manufactured using the hTERT promoter followed by genes encoding for specific proteins. The protein can be a toxin, an apoptotic factor, or a viral protein. Toxins such as diphtheria toxin interfere with cellular processes and eventually induce apoptosis.[43] Apoptotic death factors like FADD (Fas-Associated protein with Death Domain) can be used to force cells expressing hTERT to undergo apoptosis.[46] Viral proteins like viral thymidine kinase can be used for specific targeting of a drug.[47] By introducing a prodrug only activated by the viral enzyme, specific targeting of cells expressing hTERT can be achieved.[47] By using the hTERT promoter, only cells expressing hTERT will be affected and allows for specific targeting of tumor cells.[43][46][47]

Aside from cancer therapies, the hTERT gene has been used to promote the growth of hair follicles.[48]

A schematic animation for gene therapy is shown as follows.

Telomerase reverse transcriptase has been shown to interact with:

Continued here:
Telomerase reverse transcriptase - Wikipedia

IPS Cell Therapy Comments Off on Telomerase reverse transcriptase – Wikipedia | April 16th, 2017