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Human stem cell defenses activated by irradiation, study finds – Phys.Org

By adminAugust 25, 2017Stell Cell Research

August 25, 2017 Credit: MIPT

Researchers from several Russian institutes, including MIPT, have found out how prolonged exposure to ionizing radiation affects human stem cells. They discovered that it causes a cell cycle delay, which leads to faster repairs of radiation-induced DNA double-strand breaks, with fewer errors. It is unclear what the health implications are, in particular, how this affects the risk of developing cancer. The paper was published in Oncotarget.

Ionizing radiation is capable of turning neutral atoms and molecules into charged ions. The human body is inevitably exposed to natural background radiation, with an average person receiving about 3 milligrays of radiation annually. Moreover, one X-ray exam amounts to anywhere from 0.001 to 10 milligrays of additional exposure, depending on the exact procedure. That said, overexposure is dangerousa dose of more than 1,000 milligrays received within a brief period of time causes acute radiation sickness.

To ensure radiation security, it is vital to assess the risks posed by ionizing radiation. Studies of people exposed to radiation have only conclusively established the increased risk of cancer as a result of receiving a high dose of radiation. This led regulating authorities to accept a linear model under which low doses of radiation also increase the risk of cancer. However, experiments show that low-dose radiation exposure either had no adverse biological effect or was even beneficial, as evidenced by prolonged lifespans and less frequent cancer occurrence.

Apart from that, the importance of the so-called dose rate should not be overlooked. Exposure to equal doses of radiation over shorter or longer time intervals has a different effect, with "slow" irradiation causing less harm. The extent to which dose rate affects the biological outcomes is a cause of much debate. In a real-life setting, people are more likely to face prolonged exposure to low-dose radiation, so it is crucial that we understand its effects.

DNA double-strand breaks

One of the negative effects of radiation is the formation of the so-called DNA double-strand breaks, in which both strands of the double helix are severed. Fortunately, the cell is capable of repairing damaged DNA. If one of the two strands is damaged, the other can be used to repair it. However, in the case of a double-strand break, more error-prone mechanisms have to be employed. Left unrepaired or misrepaired, such lesions can give rise to oncological diseases. This explains why research into the effects of radiation on living cells tends to focus on double-strand breaks. Not long ago, it was found that stem cellsfunctionally undifferentiated cellsplay a major part in the formation of tumors by accumulating mutations and passing them on to the specialized cells that are their descendants. However, stem cell response to prolonged irradiation remains poorly understood.

The scientists conducted several experiments using stem cells derived from gingivae, or the gums. They treated the cells with identical radiation doses administered over long and short time spans. The formation of double-strand breaks was monitored using stained H2AX and 53BP1 proteins as markers. With brief but intense radiation exposure, the incidence of both markers was found to increase linearly with the dose. But in the case of prolonged irradiation, the response was linear only up to a certain point, followed by a plateau at 1,000 milligrays. In other words, after reaching a certain number, the lesion count does not continue to rise. A balance of sorts is achieved between break formation and repair.

DNA repair

The cell comes equipped with repair systems capable of mending DNA double-strand breaks. However, following intense irradiation, the cell has to resort to a mechanism known as end joininga quick but faulty procedurein eight out of 10 double-strand breaks. This often leads to chromosomal aberrations. Such misrepairs of DNA breaks can potentially result in cell death, oncogene activation, and anti-oncogene suppression. But there is an alternative mechanism of DNA repair, called homologous recombination. It uses a similar or identical DNA molecule as a template and produces far fewer errors, but it is only available during certain phases in the cell cycle. The researchers monitored homologous recombination using Rad51, another protein marker. During a two-hour long exposure, the amount of Rad51 remained roughly constant, followed by a linear growth afterward. The team hypothesized that prolonged irradiation might activate homologous recombination.

Cell division

Stem cells can be divided into two groups, called proliferating and quiescent, in which the former undergo division, the latter have ceased reproducing, and there is a balance between the two types of cells. The researchers counted the DNA double-strand breaks in proliferating and quiescent cells separately. This is made possible by a certain protein that is only found in cells undergoing division. It turned out that in both types of cells, the number of DNA breaks grew, eventually reaching a constant value.

The researchers also observed that exposure to radiation did not change the roughly four to one ratio between proliferating and quiescent cells. However, a more detailed investigation revealed that four hours of "slow" irradiation results in a considerably increased number of cells in the S and G2 phases of the cyclethat is, DNA synthesis and final preparation for division, respectively. It is during these phases that a copy of the cell's DNA is available for the sake of division, but also to be used as a template in homologous recombination. This fact is a likely explanation for the detection of increased amounts of the Rad51 marker. To put it another way, irradiation causes a delay in the cell cycleas a result, at any given time, there are more cells in those phases that enable homologous recombination. This means it is possible to repair DNA double-strand breaks correctly.

"We have shown that prolonged irradiation of mesenchymal stem cells leads to cell cycle redistribution. This might influence the biological response to radiation," says Sergey Leonov, the director of the Phystech School of Biological and Medical Physics. "Our findings could become the basis of further research into double breaks in stem cells and their effect on tumor formation."

Explore further: How breaks in DNA are repaired

More information: Anastasia Tsvetkova et al, H2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation, Oncotarget (2017). DOI: 10.18632/oncotarget.19203

A team of researchers from the biology department at TU Darmstadt has discovered that the processes for repairing DNA damage are far more complex than previously assumed. The ends of breaks in the double helix are not just ...

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Human stem cell defenses activated by irradiation, study finds - Phys.Org

Hair Loss Got You Down? Platelet-Rich Plasma May Regrow It … – Health Essentials from Cleveland Clinic (blog)

By adminAugust 25, 2017Platelet Rich Plasma Injections

Are you looking for a hair loss solution? A therapy that promotes healing in injured joints may help restore your lost hair.

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About 50 million American men and 30 million womenhave male- or female-pattern baldness. It can begin early in life, but is much more common after the age of 50, when more than 50 percent of men will experience some kind of hair loss.

However, an emerging treatment platelet-rich plasma (PRP) therapy appears to help regrow lost hair. And, there are virtually no side effects from PRP, except for a mild feeling of pressure at the injection site, saysdermatologist Shilpi Khetarpal, MD.

Physicians began using PRP therapy about a decade ago to speed up the healing process in damaged joints after injury or surgery.

During the treatment, a technician draws your blood and spins it in a centrifuge to separate out the platelets and plasma. Doctors then inject the plasma, which helps repair blood vessels, promote cell growth and wound healing, and stimulate collagen production.

Doctors began using PRP in dermatology after researchers found that high concentrations of platelets in plasma cells help promote hair growth by prolonging the growing phase of the hair cycle.

Doctors inject plasma into the scalp where hair loss has occurred. They typically administer injections monthly for three months, then spread them out over about three or four months for up to two years. The injection schedule will depend on your genetics, pattern and amount of hair loss, age and hormones.

Because the treatment is cosmetic, insurance does not cover the procedure, Dr. Khetarpal says. The cost ranges between $500 and $1,000 per injection session.

Other treatments for hair loss currently on the market are often more problematic for many patients, Dr. Khetarpal says.

There are two FDA-approved medications for treating hair loss: finasteride and minoxidil.But you must take these drugs consistently over time and results are inconsistent, she says.

Each drug also sometimes has side effects:

Hair transplantation is another option, but it requires cuts in the scalp and recovery time is longer, she says.

Because it is a surgical procedure, doctors typically recommend hair transplantation only for those who have dramatic hair loss. A transplant is also more costly and leaves scars. Doctors can perform PRP therapy prior to transplantation, which can provide better results with more dense hair growth, Dr. Khetarpal says.

Recent research bears out the potential of PRP therapy.

In a 2014 study, researchers in India looked at men with male-pattern baldness who used both approved medications, but saw little change in their hair growth.

After four PRP treatments, they had about 30 percent more growth in thinning areas.

A 2017 study out of Italy also found male patients had increased hair and density in areas where doctors used PRP therapy.

Dr. Khetarpal says it takes about three months to see an improvement. After that time, most of her patients both male and female have regrown 30 to 40 percent of the hair theyve lost.

Part of the success of PRP comes from selecting the right patients for therapy, Dr. Khetarpal says. PRP is safe and effective for many people. However, you should not have PRP therapy if you fall into either of these groups:

PRP therapy works better if your hair loss is recent. It is more challenging to wake up hair follicles that have been dormant for a long time, Dr. Khetarpal says.

I tell people I can get your hair back to what it was five years ago, she says. If your hair loss is older, you may see some recovery, but its likely not worth your investment of time and money.

Stem cell treatment for children with spina bifida helps dogs first – Phys.Org

By adminAugust 25, 2017Stem Cell Medicine

August 25, 2017 by Karen Finney An English bulldog undergoes surgery for spina bifida at the UC Davis Veterinary Medical Teaching Hospital. The dog is part of a pair of puppies being treated for spina bifida through a combination of stem cell therapy and surgery, research made possible through collaboration between the UC Davis School of Veterinary Medicine and UC Davis Health. Credit: Gregory Urquiaga/UC Davis

A pair of English bulldog puppies are the first patients to be successfully treated with a unique therapya combination of surgery and stem cellsdeveloped at the University of California, Davis, to help preserve lower-limb function in children with spina bifida.

Because dogs with the birth defect frequently have little control of their hindquarters, they also have little hope for a future. They are typically euthanized as puppies.

At their postsurgery re-check at 4 months old, however, the siblings, named Darla and Spanky, showed off their abilities to walk, run and play to their doctor, veterinary neurosurgeon Beverly Sturges.

"The initial results of the surgery are promising, as far as hind limb control," said Sturges. "Both dogs seemed to have improved range of motion and control of their limbs."

The dogs have since been adopted, and continue to do well at their home in New Mexico.

A major step toward curing spina bifida

Spina bifida occurs when spinal tissue improperly fuses in utero, causing a range of cognitive, mobility, urinary and bowel disabilities in about 1,500 to 2,000 children born in the U.S. each year. The dogs' procedure, which involved surgical techniques developed by fetal surgeon Diana Farmer of UC Davis Health together with a cellular treatment developed by stem cell scientists Aijun Wang and Dori Borjesson, director of the university's Veterinary Institute for Regenerative Cures, represents a major step toward curing spina bifida for both humans and dogs.

Farmer pioneered the use of surgery prior to birth to improve brain development in children with spina bifida. She later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs), held in place with a cellular scaffold, helped research lambs born with the disorder walk without noticeable disability.

Sturges wanted to find out if the surgery-plus-stem-cell approach could give dogs closer-to-normal lives along with better chances of survival and adoption. At 10-weeks old, Darla and Spanky were transported from Southern California Bulldog Rescue to the UC Davis veterinary hospital, where they were the first dogs to receive the treatment, this time using canine instead of human PMSCs.

Another distinction for Darla and Spanky is that their treatment occurred after birth, since prenatal diagnosis of spina bifida is not performed on dogs, Sturges explained. The disorder becomes apparent between 1 and 2 weeks of age, when puppies show hind-end weakness, poor muscle tone, incoordination and abnormal use of their tails.

A unique environment for collaborative research

UC Davis is the only place where this type of cross-disciplinary, transformational medicine could happen, according to Farmer.

"It's rare to have a combination of excellent medical and veterinary schools and strong commitment to advancing stem cell science at one institution," she said.

UC Davis is also home to the One Health initiative aimed at finding novel treatments like these for diseases that affect both humans and animals.

"I've often said that I have the greatest job on the planet, because I get to help kids," Farmer said. "Now my job is even better, because I get to help puppies too."

Hopes for clinical trials in humans and dogs

With additional evaluation and U.S. Food and Drug Administration approval, Farmer and Wang hope to test the therapy in human clinical trials. Sturges and Borjesson hope to do the same with a canine clinical trial. They hope the outcomes of their work help eradicate spina bifida in dogs and humans.

In the meantime, the team wants dog breeders to send more puppies with spina bifida to UC Davis for treatment and refinements that help the researchers fix an additional hallmark of spina bifidaincontinence. While Darla and Spanky are very mobile and doing well on their feet, they still require diapers.

"Further analysis of their progress will determine if the surgery improves their incontinence conditions," Sturges said.

Explore further: Prenatal stem cell treatment improves mobility issues caused by spina bifida

The lower-limb paralysis associated with spina bifida may be effectively treated before birth by combining a unique stem cell therapy with surgery, new research from UC Davis Health System has found.

In a study to be presented Saturday, Jan. 28, in the oral concurrent session, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, researchers evaluated a possible regenerative patch by using ...

In a study to be presented on Feb. 5 in an oral plenary session, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in Atlanta, researchers will present findings from a study titled, Cryopreserved ...

A system incorporating a smartphone app may help adolescents and young adults with spina bifida to improve their daily self-management skills, suggests a paper in the American Journal of Physical Medicine & Rehabilitation, ...

In a study to be presented today at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in Dallas, Texas, researchers will report findings that show that, for children with spina bifida, surgery ...

A gene related to neural tube defects in dogs has for the first time been identified by researchers at the University of California, Davis, and University of Iowa.

"Gut bacteria get to use a lot of our food before we do," says Federico Rey, a professor of bacteriology at the University of Wisconsin-Madison. Then we get their leftoversor their waste.

A majority of shark fins and manta ray gills sold around the globe for traditional medicines come from endangered species, a University of Guelph study has revealed.

The advent of farming, especially dairy products, had a small but significant effect on the shape of human skulls, according to a recently published study from anthropologists at UC Davis.

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Stem cell treatment for children with spina bifida helps dogs first - Phys.Org

‘Beating Heart’ Patch Offers New Hope for Desperately Ill Patients – NBCNews.com

By adminAugust 25, 2017Stem Cell Medicine

Aug.25.2017 / 10:24 AM ET

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From clot-busting drugs to bypass surgery, cardiologists have many options for treating the 700,000-plus Americans who suffer a heart attack each year. But treatment options remain limited for the 5.7 million or so Americans who suffer from heart failure, an often debilitating condition in which damage to the heart (often resulting from a heart attack) compromises its ability to pump blood.

Severe heart damage can pretty much incapacitate people, says Dr. Timothy Henry, director of cardiology at the Cedars-Sinai Medical Center in Los Angeles. You cant climb a flight of stairs, youre fatigued all the time, and youre at risk of sudden cardiac arrest.

Medication is available to treat heart failure, but its no panacea. And some heart failure patients undergo heart transplantation, but it remains an iffy proposition even 50 years after the first human heart was transplanted in 1967.

But soon, there may be another option.

A patch for the heart

Researchers are developing a new technology that would restore normal cardiac function by covering scarred areas with patches made of beating heart cells. The tiny patches would be grown in the lab from patients own cells and then surgically implanted.

The patches are now being tested in mice and pigs at Duke University, the University of Wisconsin and Stanford University. Researchers predict they could be tried in humans within five years with widespread clinical use possibly coming within a decade.

The hope is that patients will be again to live more or less normally again without having to undergo heart transplantation which has some serious downsides. Since donor hearts are in short supply, many patients experiencing heart failure die before one becomes available. And to prevent rejection of the new heart by the immune system, patients who do receive a new heart typically must take high doses of immunosuppressive drugs.

Heart transplants also require bypass machines which entails some risk and complications, says Dr. Timothy Kamp, co-director of the University of Wisconsins Stem Cell and Regenerative Medicine Center and one of the researchers leading the effort to create heart patches. Putting a patch on doesnt require any form of bypass, because the heart can continue to pump as it is.

To create heart patches, doctors first take blood cells and then use genetic engineering techniques to reprogram them into so-called pluripotent stem cells. These jack-of-all-trade cells, in turn, are used to create the various types of cells that make up heart muscle. These include cardiomonocytes, the cells responsible for muscle contraction; fibroblasts, the cells that give heart tissue its structure; and endothelial cells, the cells that line blood vessels.

These cells are then grown over a tiny scaffold that organizes and aligns them in a way that they become functional heart tissue. Since the patches would be made from the patients own blood cells, there would be no chance of rejection by the patients immune system.

Once the patch tissue matures, MRI scans of the scarred region of the patients heart would be used to create a digital template for the new patch, tailoring it to just the right size and shape. A 3D printer would then be used to fabricate the extracellular matrix, the pattern of proteins that surround heart muscle cells.

The fully formed patch would be stitched into place during open-heart surgery, with blood vessel grafts added to link the patch with the patients vascular system.

In some cases, a single patch would be enough. For patients with multiple areas of scarring, multiple patches could be used.

Inserting patches will be delicate business, in part because scarring can render heart walls thin and susceptible to rupture. Researchers anticipate that heart surgeons will look at each case individually and decide whether it makes more sense to cut out the scarred area and cover the defect with a patch or simply affix the patch over the scarred area and hope that, over time, the scars will go away.

Another challenge will be making sure the patches contract and relax in synchrony with the hearts onto which theyre grafted. We think this will happen because cells of the same type like to seek each other out and connect over time, Kamp says. We anticipate that if the patch couples with the native heart tissue, the electrical signals which pass through the heart muscle like a wave and tell it to contract, will drive the new patch to contract at the same rate.

How much would it cost to patch a damaged heart? Researchers put the price tag at about $100,000. Thats far less than the $500,000 or so it costs give a patient a heart transplant. And regardless of the cost, researchers are upbeat about the possibility of having a new way to treat heart failure.

Using these patches to repair the damaged muscle is likely to be very effective, says Henry. Were not quite there yet itll be a few years before you see the first clinical trials. But this technology may really provide a whole new avenue of hope for people with these conditions who badly need new treatment options.

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Yeargan Uses Patients Own Cells To Heal – Greater Wilmington Business Journal

By adminAugust 25, 2017Stem Cell Medicine

Austin Yeargan III is on an ongoing quest to dismantle human disease.

The orthopedic sports surgeon and regenerative orthopedist is also a husband, dad and self-described motocross and surfing athlete, who likes to keep an eye on the most up-to-date techniques in his profession.

I am most excited about discovering the simplest, most natural, least invasive and most efficacious cellular- and molecular-based treatment options for patients to keep them doing what they love, Yeargan said.

At his practice, Regenerative Medicine Clinic at 5725 Oleander Drive, he uses techniques he has brought to the rapidly expanding field of regenerative medicine and orthobiologics.

Our techniques harvest, concentrate and deploy the bodys own cells for healing. Specifically, we offer patients suffering from chronic, debilitating and often immobilizing joint pain with an alternative to traditional bone and joint surgery, including total joint replacement, Yeargan said. We have developed techniques that surgeons across the country and the world have successfully duplicated, confirming the efficacy of the treatments.

His interest in this type of treatment was rooted in an early memory.

When I was 14, I was an elite-level soccer player and contest surfer, said the Raleigh native. I broke my tibia at a soccer tournament in the spring, just after receiving a new surfboard for my birthday. When the long leg cast came off in August, my knee wouldnt bend, and the limb was atrophied. Ever since then, Ive had it in the back of my mind how ridiculous it was that modern medicine couldnt make my leg heal faster or keep my knee from becoming stiff.

He was introduced to the field by the Dan Eglinton, who practiced in Asheville. Yeargan said Eglinton was the first nationally to use biologics in orthopedic surgery for hip avascular necrosis.

After receiving his science degree in chemistry at the University of North Carolina at Chapel Hill in 1993, Yeargan attended the East Carolina University School of Medicine. He completed his general surgery internship and orthopedic surgery residency at the University of Hawaii, spending six months each at the Tripler Army Medical Center and Shriners Hospital for Children.

During his time in Hawaii, he gained additional expertise through two years of clinical and bench research, focusing on cellular and molecular level changes in thermal capsulorrhaphy and cartilage injury.

Yeargan then completed a sports medicine, adult shoulder, elbow and knee fellowship with additional hand training at The Steadman Clinic in Vail, Colorado.

During Yeargans fellowship, he worked with players on several professional sports teams, including the Colorado Rockies, Denver Broncos, Denver Nuggets and the U.S. ski and snowboard teams. (More recently, Yeargan has served as a team doctor for local high schools.)

When I returned to North Carolina in 2009, I was the first surgeon in the country to use a patients own stem cells in combination with shoulder surgery, and I witnessed firsthand the positive effects, Yeargan said. The results were extraordinary, and it was then that I realized that there was about to be a massive paradigm shift in medicine.

He said he didnt necessarily make a conscious decision to pursue regenerative medicine.

I just found that I had become a regenerative orthopedic surgeon. I was so excited to read and study immunology. I think this was the biggest advancement in my knowledge base, when I realized the potential for cellular technology to dismantle human disease, as we know it, he said.

In 2010, Yeargan introduced stem cell treatment to the area.

Thanks to new ultrasound technology and instrumentation, we have been able to narrow our focus to office procedures that are minimally invasive and can be done through a tiny, 2 [millimeter] incision and with little recovery time, he said.

He said that in some settings, genetic screening, nutrition counseling and lifestyle management planning may be offered.

All of our procedures are non-operative. Our flagship procedure is the mesenchymal signaling cell concentrate that involves harvest and processing of nucleated stem cells, dendritic cells, immune cells, endothelial cells and pericytes. Yeargan said. Bone marrow is taken easily and virtually painlessly from the pelvic crest with the patient seated comfortably. Once collected, the isopycnic separator produces three distinct layers that are processed in a proprietary fashion before administration at the target site.

The procedure may be just as valuable in a 14-year-old with a cartilage injury as it is to an 87-year-old grandmother with gonarthrosis who just wants pain relief, he added.

Human cells work by signaling, Yeargan said. We think of it like medicinal signaling cells. Signaling cells respond to the environment so just the right amount of substrate will be produced by the cell until ultimately being shut down by natural feedback loops, he said.

The clinic also offers another non-surgical option for patients suffering from Achilles tendonitis, tennis and golfers elbow and plantar fasciitis. The Tenex Tenotomy System addresses those conditions.

Biologics are ideal when combined with the percutaneous Tenex procedure for tendinitis and tendinosis in most locations and contribute to the effectiveness of the procedure, Yeargan said.

The clinics Proprietary Platelet Rich Plasma procedure, or PRP+, is used to treat acute injuries primarily. It can be used for pain in areas ranging from joints to the face.

MI-EYE is camera-in-needle technology that also can be performed routinely in the office. It allows full view of the joint space for diagnosis without having to undergo an MRI, and injection procedures can be performed at the same time without changing the portal, Yeargan said.

The clinic serves about 500 patients annually.

There is definitely a growing demand for regenerative therapies in orthopedics and in general, Yeargan said. Being one of the only orthopedic surgeons specializing in non-operative orthopedics and regenerative medicine in the state, my hope is not only to educate patients about regenerative medicine but also educate the local and regional medical community as to its advantages and patient benefits.

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Yeargan Uses Patients Own Cells To Heal - Greater Wilmington Business Journal

State’s Stem Cell Agency Awards $18.2 Million Grant for B Cell Cancer Clinical Trial – UC San Diego Health

By adminAugust 25, 2017Stem Cell Medicine

The Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine (CIRM) today unanimously approved an $18.29 million grant to University of California San Diego School of Medicine researchers to fund a phase Ib/IIa clinical trial of a novel combination drug therapy for B-cell cancers.

Scanning electron micrograph of B lymphocyte. Image courtesy of National Cancer Institute.

The approach combines an experimental monoclonal antibody-based drug called cirmtuzumab with ibrutinib, a small molecule drug that inhibits a protein called Brutons tyrosine kinase. Ibrutinib, marketed as Imbruvica, is already approved to treat B cell cancers, like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Cirmtuzumab targets ROR1, a cell surface protein present on tumors but not in normal adult tissues a distinction that makes it an attractive target for anticancer therapy. Cirmtuzumab is currently in clinical trials for the treatment of CLL.

The new combined drug trial, intended to study both safety and efficacy, is headed by Thomas Kipps, MD, PhD, Distinguished Professor of Medicine and deputy director of research at UC San Diego Moores Cancer Center, in collaboration with colleagues at the UC San Diego CIRM Alpha Stem Cell Clinic the cell therapy arm of the Sanford Stem Cell Clinical Center at UC San Diego Health.

We are very excited about evaluating this combination of targeted therapies in the clinic, said Kipps. Although ibrutinib has been approved for treatment of patients with CLL or MCL, it is exceptionally rare for this drug by itself to get rid of all the leukemia cells or cause long-lasting remissions without continuous therapy.

As a result, patients are recommended to take ibrutinib indefinitely until they develop intolerance or resistance to this drug. By blocking a survival/growth-stimulating pathway that provides a lifeline to the leukemia cells of patients taking ibrutinib, cirmtuzumab can work together with ibrutinib to potentially kill all the leukemia cells, allowing patients to achieve a complete remission and stop therapy altogether.

Kipps noted, too that cirmtuzumab targets cancer stem cells, which behave somewhat like the roots of the disease, resisting many forms of treatment and allowing a malignancy to grow back after apparently successful therapy. By targeting cancer stem cells, said Kipps, cirmtuzumab may improve our capacity to achieve more complete and longer lasting remissions when used in combination with targeted drugs, such as ibrutinib, or other anti-cancer drugs for the treatment of patients with many different types of cancer.

B cell malignancies are cancers of the blood. B cells are a type of white blood cell or lymphocyte, part of the immune system. Some B cells produce antibodies to immediately help fight off infections while others, called memory B cells, remember the pathogen in case of future infections. In B cell cancers, mutated B cells dysfunction or grow in an uncontrolled manner, resulting in diseases like CLL (the most common type of leukemia) and most non-Hodgkins lymphomas.

Cirmtuzumab was developed in Kipps laboratory under the auspices of CIRMs HALT leukemia grant awarded to Dennis Carson, MD, principal investigator, and Catriona Jamieson, MD, PhD, deputy director of the Sanford Stem Cell Clinical Center and director of stem cell research at Moores Cancer Center. Kipps led one of the six projects, generating antibodies against ROR1 that, ultimately, led to the cirmtuzumab trials in patients with CLL.

Every year around 20,000 Americans are diagnosed with CLL, said Maria Millan, MD, interim president and CEO of CIRM. For those who have run out of treatment options, the only alternative is a bone marrow transplant. Since CLL afflicts individuals in their 70's who often have additional medical problems, bone marrow transplantation carries a higher risk of life-threatening complications. The combination approach of cirmtuzumab and Ibrutinib seeks to offer a less invasive and more effective alternative for these patients.

Cirmtuzumab has also shown efficacy against solid tumors. A clinical trial is planned to test it, in combination with the drug paclitaxel, for treating metastatic breast cancer. That trial is not yet recruiting participants. Cirmtuzumabs name is a nod to CIRMs long-standing support and research funding.

CIRM was created in 2004 by California voters with $3 billion in funding support to accelerate stem cell research and treatments. Since 2004, UC San Diego researchers have received at least 96 CIRM awards, totaling more than $182 million.

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embryonic stem cells : NPR

By adminAugust 25, 2017Embryonic Stem Cells

A human embryo kept alive in the lab for 12 days begins to show signs of early development. The green cells seen here in the center would go on to form the body. This embryo is in the process of twinning, forming two small spheres out of one. Courtesy of Gist Croft, Cecilia Pellegrini, Ali Brivanlou/Rockefeller University hide caption

Four sheep cloned from the same genetic material as Dolly roam the paddocks in Nottingham, England. The University of Nottingham hide caption

Ken (left) and Henry were created using DNA plucked from a skin cell of Melvin, the beloved pet of Paula and Phillip Dupont of Lafayette, La. Edmund D. Fountain for NPR hide caption

In 1954, Dr. Frederick C. Robbins, then chief of pediatrics and contagious diseases at Cleveland Metropolitan General Hospital, was one of three winners of that year's Nobel Prize in medicine. The scientists' work, which led to a vaccine against polio, was performed in human fetal cells. AP hide caption

Ryoji Noyori, a Nobel Prize-winning chemist and president of Japan's prestigious RIKEN research institute, bows at a news conference in Tokyo Tuesday to apologize for the scientific misconduct of a RIKEN colleague. Eugene Hoshiko/AP hide caption

A mouse embryo grows from stem cells made by stressing blood cells with acid. The blood cells are tagged with a protein that creates green light. Courtesy of Haruko Obokata hide caption

After President Obama overturned Bush-era policy restricting federal funding of embryonic stem cell research in 2009, Nebraska Right to Life led a protest of the research outside the University of Nebraska regents' meeting. Nati Harnik/AP hide caption

Human embryos grow in a petri dish two days after scientists in Oregon cloned them from a donor's skin cell. http://www.flickr.com/photos/ohsunews/8726915230/in/photostream//Courtesy of OHSU Photos hide caption

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embryonic stem cells : NPR

Mouse model of human immune system inadequate for stem cell studies – Stanford Medical Center Report

By adminAugust 25, 2017Embryonic Stem Cells

In an ideal situation, these humanized mice would reject foreign stem cells just as a human patient would.

Wu shares senior authorship of the research, which was published Aug. 22 in Cell Reports, with Dale Greiner, PhD, professor in the Program in Molecular Medicine at the University of Massachusetts Medical School, and Leonard Shultz, PhD, professor at the Jackson Laboratory. Former postdoctoral scholars Nigel Kooreman, MD, and Patricia de Almeida, PhD, and graduate student Jonathan Stack, DVM, share lead authorship of the study.

Although these mice are fully functional in their immune response to HIV infection or after transplantation of other tissues, they are unable to completely reject the stem cells, said Kooreman. Understanding why this is, and whether we can overcome this deficiency, is a critical step in advancing stem cell therapies in humans.

Humanized mice are critical preclinical models in many biomedical fields helping to bring basic science into the clinic, but as this work shows, it is critical to frame the question properly, said Greiner. Multiple laboratories remain committed to advancing our understanding and enhancing the function of engrafted human immune systems.

Greiner and Shultz helped to pioneer the use of humanized mice in the 1990s to model human diseases and they provided the mice used in the study.

The researchers were studying pluripotent stem cells, which can become any tissue in the body. They tested the animals immune response to human embryonic stem cells, which are naturally pluripotent, and to induced pluripotent stem cells. Although iPS cells can be made from a patients own tissues, future clinical applications will likely rely on pre-screened, FDA-approved banks of stem cell-derived products developed for specific clinical situations, such as heart muscle cells to repair tissue damaged by a heart attack, or endothelial cells to stimulate new blood vessel growth. Unlike patient-specific iPS cells, these cells would be reliable and immediately available for clinical use. But because they wont genetically match each patient, its likely that they would be rejected without giving the recipients immunosuppressive drugs.

Humanized mice were first developed in the 1980s. Researchers genetically engineered the mice to be unable to develop their own immune system. They then used human immune and bone marrow precursor cells to reconstitute the animals immune system. Over the years subsequent studies have shown that the human immune cells survive better when fragments of the human thymus and liver are also implanted into the animals.

Kooreman and his colleagues found that two varieties of humanized mice were unable to completely reject unrelated human embryonic stem cells or iPS cells, despite the fact that some human immune cells homed to and were active in the transplanted stem cell grafts. In some cases, the cells not only thrived, but grew rapidly to form cancers called teratomas. In contrast, mice with unaltered immune systems quickly dispatched both forms of human pluripotent stem cells.

The researchers obtained similar results when they transplanted endothelial cells derived from the pluripotent stem cells.

To understand more about what was happening, Kooreman and his colleagues created a new mouse model similar to the humanized mice. Instead of reconstituting the animals nonexistent immune systems with human cells, however, they used immune and bone marrow cells from a different strain of mice. They then performed the same set of experiments again.

Unlike the humanized mice, these new mice robustly rejected human pluripotent stem cells as well as mouse stem cells from a genetically mismatched strain of mice. In other words, their newly acquired immune systems appeared to be in much better working order.

Although more research needs to be done to identify the cause of the discrepancy between the two types of animals, the researchers speculate it may have something to do with the complexity of the immune system and the need to further optimize the humanized mouse model to perhaps include other types of cells or signaling molecules. In the meantime, they are warning other researchers of potential pitfalls in using this model to screen for immunosuppressive drugs that could be effective after human stem cell transplants.

Many in the fields of pluripotent stem cell research and regenerative medicine are pushing the use of the humanized mice to study the human immune response, said Kooreman. But if we start to make claims using this model, assuming that these cells wont be rejected by patients, it could be worrisome. Our work clearly shows that, although there is some human immune cell activity, these animals dont fully reconstitute the human immune system.

The researchers are hopeful that recent advances may overcome some of the current models limitations.

The immune system is highly complex and there still remains much we need to learn, said Shultz. Each roadblock we identify will only serve as a landmark as we navigate the future. Already, weve seen recent improvements inhumanized mousemodels that foster enhancement of human immune function.

Wu is a member of Stanford Bio-X, the Stanford Cancer Institute and the Stanford Child Health Research Institute. He is also the Simon H. Stertzer Professor.

Additional Stanford co-authors are former research assistant Raman Nelakanti; former postdoctoral scholars Sebastian Diecke, PhD, and Veronica Sanchez-Freire, PhD; postdoctoral scholar Ning-Yi Shao, MD, PhD; instructor Elena Matsa, PhD; and associate professor of pathology Andrew Connolly, MD, PhD.

The research was funded by the California Institute of Regenerative Medicine, the National Institutes of Health (grants R01HL132875, R01HL133272, P30CA034196, UC4DK104218 and T32OD01112) and the Helmsley Charitable Trust.

Stanfords Department of Medicine also supported the work.

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Mouse model of human immune system inadequate for stem cell studies - Stanford Medical Center Report

Injections of Vitamin C Could Help Fight Blood Cancer – Wall Street Pit

By adminAugust 25, 2017Embryonic Stem Cells

According to the Leukemia & Lymphoma Society (LLS), one person in the United States is diagnosed with a blood cancer every 3 minutes. One person dies approximately every 9 minutes due to this illness.

Blood cancers affect the blood, bone marrow, and lymphatic system. Most of these cancers originate in the bone marrow where new blood cells are produced. .

Our bone marrow produces three types of blood cells: red blood cells, white blood cells, and platelets. However, cancer in the blood occurs when an abnormal type of blood cell goes into an uncontrolled growth and disrupts the normal blood cell development.

The three main types of blood cancers are:

Now, theres news that vitamin C can help fight blood cancer.

Luisa CimminoandBenjamin Neelat the New York University School of Medicine and their colleagues have discovered that, by injecting vitamin C, cancer growth could be prevented.

According to the researchers, blood cancers like acute and chronic leukemia are caused by the mutation of a gene called tet methylcytosine dioxygenase 2 or TET2. This gene is responsible for ensuring the healthy growth of certain stem cells for the production of white blood cells. But, when TET2 mutation occurs, cell growth goes haywire and leads to cancer.

In their mice experiment, the animals were given variableTET2function through genetic engineering. The researchers discovered that cancer is induced with 50 per cent reduction in TET2 activity, and it continues to develop when the said gene remained at a low level.

However, when TET2 was restored, the gene stopped the uncontrolled growth and killed the cancerous cells.

After such findings, what the team needed to find next was something to reactivate TET2. And they opted to use vitamin C, which has the potency to affect embryonic stem cells.

For 24 weeks, they injected a group of mice which had low TET2 with very high dose of vitamin C daily. This slowed the progression of blood cancer. But, in the case of another group of mice which did not receive vitamin C injections, they showed signs of developing leukemia.

Moreover, to test the efficacy of vitamin C, the researchers added it to a cancer drug to which they exposed human leukemia cells in a lab dish. It proved very effective.

With this discovery, the team is hoping that vitamin C would be used in cancer therapies. It would especially help older people with blood cancer whose immune system are too weak to undergo chemotherapy. But, this would have to be done intravenously. Just taking in large doses of vitamin C would not prevent cancer since the body excretes it through urine when its already above 500 milligrams.

Still, this is a very important study that will definitely have a very lasting impact on the field, notes Ulrich Steidl of the Albert Einstein College of Medicine, adding that it will likely inspire a lot of scientists and translational investigators to think about similar strategies and to go after these pre-leukemic stem cells, which, in [Steidls] opinion will be critical if were ultimately aiming for a cure.

For healthy people, or those who want to boost their immune system, experts recommend taking vitamin C supplements twice a day for better absorption.

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Injections of Vitamin C Could Help Fight Blood Cancer - Wall Street Pit

Stem cell therapy: proffering hope for special needs patients … – BusinessDay (satire) (press release) (registration) (blog)

By adminAugust 25, 2017Stem Cell Treatment

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

Kemi Ajumobi