Thu, Mar 23

Promising Early Stem Cell Trial Results: Hold Steady

By Center for Regenerative Medicine centerforregmedmc

This story was previously published in Mayo Clinic Magazine.

Steve Day is on a mission as he scans a crowd of about 150 people in the banquet hall of a golf course in his boyhood hometown of Sioux Falls, South Dakota. When he finally finds his target, he begins weaving through the crowd. Steve’s cane and wobbly amble are the only signs that something might be amiss with the retired grandfather.

“Hi, Coach,” Steve says. “Steve Day? I can’t believe it’s you, and you’re here,” says David Kinney, Steve’s former wrestling coach who last talked to his Lincoln High pupil in 1969. Sometimes, Steve can’t believe he’s standing here either, in the aftermath of a diagnosis he formally received a little over three years ago at Mayo Clinic in Rochester, Minnesota. Steve’s balance issues, sleeping problems and irregular blood pressure stem from a rare, unusual neurodegenerative disease — multiple system atrophy.

Looking Back
With hindsight, it’s easy for Mary, Steve’s wife and a physical therapist, to spot signs of her husband’s then-worsening balance.

“When we look back now, we walked the Kalalau Trail in Hawaii in 2010, and there were many times I was really nervous,” she says. “It’s a narrow trail and it’s very uneven. While he didn’t fall, his balance wasn’t what it used to be. But, we didn’t think anything more of it at the time.” In the ensuing months after returning home to Denver from their favorite vacation spot, Steve began to fall. First the slips came on uneven ground at job sites where he worked as a geotechnical engineer. But eventually, he was no safer on flat ground. Doctors thought they’d figured it out when he visited a neurologist in 2012 who discovered Steve needed neck surgery to correct a condition that caused him to lose feeling in his left arm. Steve was told the balance issues should correct themselves in 12 to 18 months. Instead, they got progressively worse.

Finally, an MRI showed something concerning in early 2013 — atrophy of the cerebellum and pons areas of Steve’s brain that control muscle function and involuntary (autonomic) functions. His doctors in Colorado told him there wasn’t anything they could do to slow the progression. When Mary requested a referral for a second opinion at Mayo Clinic, they still didn’t have a name for the condition. All they had were signs that it was advancing beyond control. “I was falling more and more before I went to Mayo Clinic,” Steve says.

Wolfgang Singer, M.D., and Phillip A. Low, M.D.,
are studying how to best help people with multiple system atrophy using regenerative medicine techniques.

‘This Is Not Right’
Multiple system atrophy (MSA) is a rare neurological disorder that impairs a person’s involuntary functions, including blood pressure, heart rate, bladder function and digestion. People begin showing symptoms of the degenerative disease in their 50s or 60s. “It’s a rare disease,” says Mayo Clinic neurologist Wolfgang Singer, M.D., who estimates the institution sees about 15 new patients with MSA each month. “Typically, the story is that patients have seen several neurologists or even cardiologists because they’ve fainted. “Eventually, someone says, ‘This is not right; this is not Parkinson’s disease. Let’s get you to a center that has more experience.’ And they come here not knowing the diagnosis.” That moment of diagnosis can be even worse — MSA is terminal and treatment options focus on managing the myriad of symptoms. “This is a rapidly and relentlessly progressive disease,” Dr. Singer says. “The median survival is less than three years from the time diagnosis is made, seven to eight years from the first symptom. Today, there is no treatment to slow the disease course.”

‘I Was Resigned’
Before Steve even traveled to Mayo Clinic, his local neurologist gave him discouraging news. “She said, ‘You’re eventually going to choke to death,’” Steve recalls. “I was resigned to it already.” But Mary was determined to see if Mayo Clinic had any ongoing research for conditions like Steve’s.

When they met neurologist Joseph Y. Matsumoto, M.D., he first suspected Steve might be experiencing MSA and referred them to Dr. Singer. “Dr. Matsumoto said, ‘I want Dr. Singer to look at your tests,’ which all came back not good, and we met with Dr. Singer within an hour,” Mary recalls. “We had been told previously in Denver there was nothing to be done, just go home.”

Steve Day participated in a research study at Mayo Clinic to try to slow the progression of multiple system atrophy.

Even Slowing Is Big
For as rapid and relentless as MSA is, Dr. Singer and neurologist Phillip A. Low, M.D., have been working for the past five years on a leading-edge regenerative medicine approach to manage the disease progression by using adult stem cells procured through the patient’s own fat cells. An early-stage trial of 24 people with MSA, including Steve, began in 2013. Dr. Singer says, “Most patients receiving this experimental treatment experienced a slower progression than MSA patients who did not receive stem cells. It’s a highly significant result.” The final follow-up of the patients ended in the summer of 2016.

The participants were so grateful to have participated in the study they asked Dr. Singer what was next after the first year of injections. Drs. Singer and Low petitioned the Food and Drug Administration to allow them to continue injecting adult stem cells every six months under compassionate care protocols. Every participant offered the ability to continue the treatments did so. “We also want to make it clear to patients, this is not a cure,” Dr. Singer says. “Patients still progress, but it seems to be something that slows the disease course. Looking at neurodegenerative disorders, we don’t have anything like this. Even slowing is a big thing.” Steve and Mary say while they hope for a cure, it’s been made very clear to them that Steve’s condition will progress. “In the excitement of seeing good results, we had to keep saying, ‘This isn’t a cure; this isn’t a cure,’” Mary says. “We’re aware that it’s not a cure, but we take what we’ve got because there is nothing else available.”

Steve and Mary estimate his first symptom appeared more than six years ago. Steve remains able to walk — a major marker in the disease’s progression — and still participates in activities such as Pilates and paddling with the Hanalei Canoe Club twice a week when they’re vacationing in Hawaii. “We just go on,” Mary says. “We don’t spend a lot of time thinking about MSA.” Dr. Singer plans to launch a larger five-year multicenter trial of 90 participants in the near future and believes the earlier in the diagnosis they can find participants, the better patients will respond to the stem cell injections. “The next phase trial will be very expensive, and we will need additional resources to support it,” Dr. Singer says. “This line of research can make an impact on the lives of our patients.”

Small Cells, Large Impact
In the trial, Drs. Singer and Low work with Mayo Clinic’s Center for Regenerative Medicine and the Human Cellular Therapy Laboratory, run by Allan B. Dietz, Ph.D., to produce the cellular therapy for study participants. These specialized cells, known as mesenchymal stem cells, are derived from the patient’s own fat tissue and cultured in the laboratory to doses of 10 million to 100 million cells per injection. For the MSA study, like nearly all cases using stem cells, this regenerative therapy is intended for people for whom there are no other treatment options available. The Human Cellular Therapy Laboratory ensures all cell therapies for early-phase clinical trials at Mayo Clinic are of the highest quality and comply with Good Manufacturing Practice regulations.

“The lab does all the hard work,” Dr. Singer says. “We came up with the idea for the study, we do the tests and the procedures surrounding the study, but the actual product is made by the Human Cellular Therapy Laboratory. We certainly couldn’t do it without them.” Another Day Back in South Dakota, Steve, his old coach and his wrestling team are being inducted into the Lincoln High School Hall of Fame for their role in an event that took place 47 years earlier — one in which they didn’t even participate. Steve and his teammates were among the best in the state in 1969. But, they never got the opportunity to wrestle for a state championship because of a February snowstorm that stranded the team and many other Sioux Falls wrestlers on an icy highway 10 miles from the arena.

Steve, wrestling at 154 pounds at the time, didn’t make it to the weigh-in on time and was disqualified, along with the rest of his Lincoln High teammates. The local newspaper dubbed the school’s disqualification “The State Title That Wasn’t.” Without a hint of snow on a balmy autumn night, Steve and the rest of his teammates reminisce and reflect on the past. While he may have missed his shot at a state title in 1969, he certainly hasn’t let any more opportunities pass him by. Steve continues looking forward. He’ll return to Hawaii soon, spend more time with his two children and two grandchildren, practice Pilates in a sun-swept studio near the Pacific Ocean and paddle again with the Hanalei Canoe Club. MSA has threatened multiple times to throw him off balance, but with the help he found at Mayo Clinic, Steve continues to have time with something that holds him steady — the life he loves. “I keep busy,” Steve says. “That’s for sure.”

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Tags: Center for Regenerative Medicine, clinical trial, Dr Low, Dr Singer, mayo clinic, medical research, MSA, multiple system atrophy, stem cells

Thu, Mar 16

Regenerative Medicine: From Blueprint to Build Out

By Center for Regenerative Medicine centerforregmedmc

Regenerative Medicine is an Established Priority at Mayo Clinic

Five years is a short amount of time to expect results from a new strategic initiative at a complex organization. But early results were evident at the Mayo Clinic Symposium on Regenerative Medicine and Surgery.

Mayo Clinic experts in regenerative medicine highlighted advancements in cancer care, cardiovascular disease, neurological conditions and musculoskeletal regeneration. More than 60 presenters from Mayo Clinic and Arizona State University shared results ranging from preliminary research to advanced discoveries in tissue engineering, cell-based therapies and cell-free therapies. The agenda included technical presentations that showed the expansive number of regenerative therapies being researched, translated and applied to patient care. The Symposium was moderated by the Center for Regenerative Medicine deputy director of education Richard Hayden, M.D.

More than cell-based therapies, regenerative medicine means to replace, engineer or regenerate cells, tissues or organs in order to restore or establish normal function. Regenerative therapies aim to amplify the body’s ability to heal itself, providing overall better health and quality of life.

Bernard Siegel, executive director of the Regenerative Medicine Foundation said in his keynote address that Mayo Clinic represents where the rubber meets the road as a large medical practice and the research that is going to impact the human population.

“Mayo Clinic has the credibility, the numbers, and the prestige to be the game changer.” says Siegel. “Mayo Clinic is going to be the institution that the world looks to as you incorporate these potentially curative technologies into the day-to-day medical practice.”

David Lott, M.D., Mayo Clinic laryngeal surgeon, discusses his research live at the Mayo Clinic Symposium on Regenerative Medicine and Surgery:

Support for Complex Tasks

Dennis Gastineau, M.D., hematologist and director of the Nyberg Human Cellular Therapy Laboratory in Arizona described the HCTL as one of the key platforms that has expanded and matured enterprise-wide. In addition to the Mayo Clinic initiated trials, the cell pharmacy is supporting 18 active protocols and an additional 25 trials are in the development stage.

“Mayo is developing a set of platforms and expertise with the idea that it is the needs of the patients we are serving,” says Dr. Gastineau. “But we also have the science. That is the advantage, and it is tremendous in that respect.”

Three platforms have emerged to accelerate the development of regenerative medicine based applications at Mayo Clinic: the Biotrust, the Biomaterials and Biomolecules Facility, and the Advanced Product Incubator. In a panel discussion, the platform directors talked about the ability to move products between the facilities during development.

Dennis Wigle, M.D., Ph.D., thoracic surgeon and deputy director for the Center for Regenerative Medicine Biotrust says the vision has always been to function as a network hub within Mayo Clinic.

“One of the goals is to be an accelerator in the development of regenerative medicine applications and to be a connector of people, ideas, and processes,” Dr. Wigle says. “Rather than being a single person in an isolated lab struggling through how to adopt some of these technologies, investigators are able to leverage the know-how and the infrastructure of the institution.”

Co-directors for the Biomaterials and Biomolecules Facility, neurologist Anthony Windebank, M.D. and orthopedic surgeon Michael Yaszemski, M.D., Ph.D., discussed the value of being involved as physicians on small phase I clinical trials to establish patient safety.

“The idea of being able to make a biomaterial based device in-house and move forward to in-person and in-clinic use is clearly very important,” says Dr. Windebank. “As we get closer to making more complex devices it will be possible to work with one or two or even three platforms with an integrated oversight of our Good Manufacturing Practice facilities.”

Atta Behfar, M.D., Ph.D , director of the Advanced Product Incubator says to think about working with the platforms for phase I trials with an eye towards phase II and III development.

“At this point, our target is getting the safety studies established and accomplished at Mayo Clinic.” says Dr. Behfar. “The long term aim is to build up the systems for later phase trials in partnership with industry.”

From the clinical perspective, orthopedic physician Shane Shapiro, M.D. said the real benefit is being able to work with experts like Dr. Behfar on potential products for the practice.

“It allows us to develop these products together,” says Dr. Shapiro. “When we demonstrate what our problem is on a foundational level, we can advance the practice and advance the use of the products to the patients who need them.”

Dr. Shapiro live from the Mayo Clinic Symposium on Regenerative Medicine and Surgery:

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Tags: advanced product incubator, biomaterials, biotrust, Mayo Clinic research, Mayo event, medical research, regenerative medicine, regenerative medicine symposium, stem cells

Sat, Mar 4

Stem Cells in Space

By Center for Regenerative Medicine centerforregmedmc

On February 19, the latest rocket launch from NASA’s Kennedy Space Center in Cape Canaveral, Florida, included a payload of several samples of donated adult stem cells from a research laboratory at Mayo Clinic’s Florida campus. The launch by SpaceX, an American aerospace manufacturer and space transport services company, is part of NASA’s commercial resupply missions to the International Space Station.

The biological cells come from the laboratory of Abba Zubair, M.D., Ph.D., who specializes in Transfusion Medicine and Regenerative Medicine. Dr. Zubair is leading regenerative medicine research to determine if healthy mesenchymal and hematopoietic stem cells, derived from the body’s bone marrow, can be mass-produced in the low-gravity environment of outer space. If the stem cells maintain their properties as they divide copiously in microgravity, they may be usable in the treatment of stroke.

Studies conducted in microgravity simulators on Earth (specifically, tanks of rotating fluid), have shown stem cells can overcome their highly restricted expansion in a buoyant environment. It’s not known why microgravity affects cell division, Dr. Zubair says, but some researchers have speculated the conditions might be similar to the floating environment of developing cells in the body. Of particular significance to Dr. Zubair is how the cells hold up in space. On the International Space Station, experiments will provide information about gene expression in the expanded cells, real-time analysis of the cell cycle, and details about molecular changes that occur. Frozen cells will undergo further testing when they return to Earth, to determine whether microgravity produces stem cells that are functional and safe to treat the swelling and inflammation that occur in stroke.

“Stem cells are known to reduce inflammation,” he explains. “We’ve shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels.” A problem in the development of stem cell therapy is that as many as 200 million cells are needed to treat a human being, and expanding vast numbers of stem cells on Earth can take weeks. “We may discover proteins or compounds that are produced that we can synthesize on Earth to encourage stem cell growth without having to go to microgravity,” Dr. Zubair says.

Four years ago, under the auspices of the Mayo Clinic Center for Regenerative Medicine, Dr. Zubair applied for research proposals that involved medicine and outer space. His mother had died of stroke in 1997, and he had been thinking about stem cells as a treatment for stroke-related brain injury.

Collaborating with Mayo Clinic neurologists James Meschia, M.D., and William D. Freeman, M.D., he studied mouse models of stroke. With funding from the Center for the Advancement of Science in Space, a nonprofit organization, he hopes to find that, in space, stem cells can be reproduced in large, safe quantities, providing new opportunities for patients. Experiments on the expanded stem cells will continue once they return to Earth.

“We’ll study them to make sure they’re normal, functional and safe for patients with stroke,” Dr. Zubair says. “My work in regenerative medicine has always been intentionally translational — not just to study what the cells do and what can be done with them but to make a difference for patients. That’s what makes our project unique.”

“At Mayo Clinic, research drives everything we do for patients,” says Gianrico Farrugia, M.D., vice president, Mayo Clinic. “This space cargo carries important material for research that could hold the key for developing future treatments for stroke — a debilitating health issue. Research such as this accelerates scientific discoveries into breakthrough therapies and critical advances in patient care.”

For the launch, Mayo Clinic is collaborating with the Center for Applied Space Technology (CAST) in Cape Canaveral, and BioServe Space Technologies in Boulder, Colorado. CAST supported Dr. Zubair's research during proposal development and served as an interface between the research team and various space hardware agencies. BioServe provided space flight hardware, on orbit research protocol and scheduling interface.

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Tags: Abba Zubair, mayo clinic, Mayo Clinic in Florida, mayo clinic medical research, Mayo Clinic research, regenerative medicine, research, space, stem cells

Wed, Feb 22

Hypoplastic Left Heart Syndrome Collaboration: Bringing Innovative Cell-Based Therapies to Patients

By Center for Regenerative Medicine centerforregmedmc

Mayo Clinic’s Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) and Children’s Hospital of Philadelphia recently announced a collaboration to delay and prevent heart failure from HLHS, a rare and complex form of congenital heart disease in which the left side of a child's heart is severely underdeveloped.

The collaboration is part of a consortium across the nation and will allow for a decrease in the amount of time from research and discovery to the clinical application of innovative cell-based therapies. The consortium aligns regional centers into a nationwide collaboration led by the Todd and Karen Wanek Family Program for HLHS at Mayo Clinic to accelerate innovation on hypoplastic left heart syndrome, discovery sciences, and clinical expertise by investing local resources back into research. The program seeks to work with five to seven regional centers across the U.S. to fund the development of cell-based innovative research opportunities to transform the lives of people living with hypoplastic left heart syndrome.

“By entering into this collaboration, we are making it possible for all children with hypoplastic left heart syndrome to be able to participate in cell-based treatments, no matter their location,” says Timothy Nelson, M.D., Ph.D., director, Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome.

Today, standard treatment for people with HLHS includes a three-stage surgery that enables the right ventricle to pump blood to the entire body. Though effective, these surgeries are palliative and do not eliminate the risk of needing a heart transplant later.

Regenerative medicine strategies for HLHS have the potential to provide an alternative to heart transplantation. Using stem cells of different types and from various sources — including cells from the patient's own body — regenerative therapies for HLHS could replace, rejuvenate or regenerate defective tissues, leaving new, healthy tissues in their place.

To learn more, visit the Mayo Clinic’s Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome website or read the news release announcing the collaboration.

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Tags: collaboration, HLHS, Hypoplastic Left Heart Syndrome, mayo clinic medical research, Mayo Clinic research, regenerative medicine, stem cells, Tim Nelson

Fri, Feb 17

The Countdown is on: Stem Cells Heading to Space

By Center for Regenerative Medicine centerforregmedmc

Previously published on the Mayo Clinic News Network.

Stem cell research is about to get a boost that’s out of this world. If all goes as planned, the SpaceX CRS-10 mission will blast off from NASA's Kennedy Space Center in Titusville, Florida this weekend to resupply the International Space Station. There will also be something extra in the payload: human adult stem cells.

After more than three years of planning and preparation, and with technical assistance provided by the Center for Applied Space Technology, Dr. Abba Zubair, a Mayo Clinic stem cell biologist is finally taking his quest for answers into orbit.

Dr. Zubair says, "We know stem cells grow differently using simulated microgravity. Primarily, our focus is to see if microgravity actually can help stem cells to expand faster, so that we can grow more of them to bring back to use for human application.” Here’s Dennis Douda for the Mayo Clinic News Network:

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Tags: Abba Zubair, mayo clinic, Mayo Clinic in Florida, mayo clinic medical research, regenerative medicine, stem cells

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