Stem Cell Clinic

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

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.

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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

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

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

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