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Thu, Sep 7 5:00am · Serving Where Needed

This story first appeared in Mayo’s research magazine, Discovery’s Edge.

Michael Yaszemski, M.D., Ph.D.

Orthopedic surgeon Michael Yaszemski, M.D., Ph.D., dressed in his scrubs, glanced through the window to the operating room. The patient lay unconscious on the table, draped and ready for the doctor to begin surgery. But at that moment an odd sensation passed through Dr. Yaszemski’s head, unlike anything he had ever experienced.

“I suddenly became aware that something bad had happened inside my head,” Dr. Yaszemski recalls now, 10 years later. “I turned around, I told one of the colleagues, ‘I’m in trouble. I need help right now.’”

Dr. Yaszemski passed in and out of consciousness during the next two days. He recalls a priest performing last rites at his bedside. He had suffered a brain hemorrhage, of unknown cause. The doctors who operated on him told him mortality for that kind of event is 50 percent.

“I flipped a coin and it stayed up on the living side,” Dr. Yaszemski says. “Anytime I feel my temper want to rise, I just think about the day I said goodbye to my wife and got the last rites. All of a sudden what I have in front of me doesn’t seem like too much of a problem. Nothing bothers me anymore.”

Surviving, Thriving
While his equanimity and humility are Dr. Yaszemski’s hallmark among his surgical staff and research colleagues, they’ve also helped him be a part of and lead high-functioning medical teams. A nationally renowned spinal surgeon, chemical engineer, and retired Air Force brigadier general, he is a widely-published researcher in the fast-evolving field of regenerative medicine. And he was recently elected to the prestigious National Academy of Medicine.

“His leadership abilities kind of naturally come through in settings where he is able to effectively cross-collaborate, get people to work as a team and do that in the interest of promoting the best care for his patients,” says Dr. Mark Pagnano, M.D., Mayo’s chair of orthopedics. “Dr. Yaszemski is definitely someone who knows how to build an effective team. He’s demonstrated that in the surgical arena and in the research arena as well.”

Surgeon, Engineer
Dr. Yaszemski spends roughly half his time as an orthopedic surgeon, and the other half as a researcher in regenerative medicine, a discipline directed to helping the body to heal itself. As director of the Tissue Engineering and Biomaterial Laboratory, he supervises 16 researchers, students and technicians as they design polymer scaffolds.

Polymer scaffolds, like the one pictured here, provide a base and guide to encourage the regrowth of bone, nerves, and cartilage.

These scaffolds provide a base and guide to encourage the regrowth of bone, nerves, and cartilage to repair a severe injury from an accident or illness such as cancer. It’s hoped that regenerative tissue growth will reduce the need for metal splints to stabilize the spine and allow for the regrowth of nerves to restore feeling and function.

“You can design a polymer to do many different things,” says Dr. Yaszemski.

He explains that the scaffolds may be formulated to be strong and rigid, providing a platform for the regrowth of bone. The polymers may also be injected as a liquid and then harden to fill a cavity. Tubular scaffolds that look like a flexible drinking straw can guide the regrowth of nerve cells and then biodegrade. And to encourage cell growth, polymers may be embedded with minerals or biological molecules or even with an electric charge.

“It’s all about the cells,” he says. “The goal here is to make a scaffold that will attract and have these cells anchored to it and give them the signals they need to start making the tissue you want them to make.”

Dr. Yaszemski learned much of what he knows about polymers before he ever imagined a medical career. “I never thought in my wildest dreams that 40 years later I’d be making polymers to put into people.”

His journey into medicine remains something of a mystery, even to him.

Decisions, Decisions
Son of a New York police officer, Dr. Yaszemski grew up in New Jersey and graduated from Lehigh University with a bachelor’s in chemistry. He entered graduate school on an NCAA scholarship — for which his college football coach had applied on his behalf without Dr. Yaszemski’s knowledge. “This,” he says, “was one of those unexpected opportunities.”

As a master’s student, he produced polymers as part of an antibody drug complex. “Of course, I didn’t have the slightest idea of what medicine was about. Maybe that got me interested. I don’t know. It was nothing I planned for,” he says.

Nonetheless, after his master’s, he went to work for the roofing manufacturer GAF Corp. “I was happy being an engineer,” he says. He was married, and his wife entered Georgetown Law School. “For reasons I don’t understand 40 years later, I sent an application into one school, Georgetown Medical School, and got in. Maybe I just wanted to be with my new wife.”

His uncle, in the Air Force, called. Dr. Yaszemski recalls the conversation like this: “Nephew, congratulations. I hear you got into medical school. How are you paying for it? I know you and your wife can’t afford it, and your parents can’t afford it. We’ve got this new program in the Air Force called Health Professions Scholarship Program. I’ve taken the liberty of getting an application and mailing it to you. I suggest you read it, fill it out, and send it in.” The Air Force paid for medical school.

Engineer, Surgeon, General… And More
“Once I got in I was hooked,” Dr. Yaszemski says. “This commitment to service, this commitment to excellence, and this insistence on integrity rang a bell with me that I never thought would be part of the military.”

Stationed at Lackland Air Force Base in San Antonio, he became a surgeon while also earning a Ph.D.

Dr. Yaszemski left active duty and was recruited by Mayo Clinic in 1996. He remained in the reserves, performing surgery in tent hospitals during tours at Balad Air Base in Iraq and Bagram Airfield in Afghanistan in 2005 and 2006.

Anthony Windebank, M.D.

Anthony Windebank, M.D., a Mayo Clinic neurologist working with Dr. Yaszemski  says the lessons of war added to Dr. Yaszemski’s abilities. “Seeing young people with severe limb damage from bullets that conventional techniques can’t repair drives part of his desire to ask what can we do better to serve these young people. I think the other way it contributes to his medical career is that he is incredibly well organized in terms of getting people to do what needs to be done to get the job done. He strongly believes the team works best when the team works together.”

Despite his achievements, Dr. Yaszemski continues to be known for his soft-spoken humility. He often avers that each of us is replaceable.

When he was read the last rites ten years ago and whisked from the operating room to an emergency room as a patient, the other surgeons had to decide what to do with the patient who was already prepped and anesthetized. After consulting with the patient’s family, another surgeon stepped in to complete the operation. And that’s how it should be according to Dr. Yaszemski.

“We are all expendable—in a second,” says Dr. Yaszemski. “We go away, and if the job we’re doing is an important job, someone else will be doing it.”

Developing polymers for bone, nerve grafts

Lichun Lu, Ph.D., a Mayo Clinic bioengineer, is developing polymers – multiple-molecule materials – that help bones regenerate and nerves grow. She and her team combine mathematics, physics and chemistry, along with biochemistry and biology so the biomaterials they make  match aspects of the human tissue they are meant to replace.

The team has come up with a pair of polymers that, when placed around a damaged vertebra, grow to be just the right size and shape to support the spinal column. To use the polymers, a surgeon would open a sterile package holding a tiny hollow tube made of an absorbent, biodegradable polymer (a hydrogel), place it within the spinal column and then douse it in saline for about five minutes, tweaking its position as it expands to bridge the gap left by a missing piece of vertebra. Next, the tube-shaped mold would be filled with a second polymer, an injectable bone cement.

“This material is much stronger, and it can be engineered either to stay in place indefinitely, or to be seeded with cells and growth factors [to help bones regenerate] and to biodegrade over time, ” explains Dr. Lu.

Electrical charge has a significant effect on growing nerves, so Dr. Lu is partnering

Andre Terzic, M.D., Ph.D.

with Anthony Windebank, M.D., to create positively charged hydrogels for conduits that stimulate and guide neuroregeneration in the body.

In collaboration with Andre Terzic, M.D., Ph.D., and others, she is strengthening these conduits for neural tissue engineering by embedding them with carbon graphene, a material stronger than steel.

And in a multiteam effort to help patients with severed spinal cords, Dr. Lu is working with Dr. Yaszemski to build scaffolds that work with the strengthened conduits. These scaffolds will be seeded with cells, growth factors, and drug-releasing microspheres, made out of yet another new polymer.

Setting the stage for new treatments 

Alexandra Greenberg, Ph.D., is a scientific casting director. She helps turn discoveries into new treatments by connecting the people, ideas and processes within the Biomaterials and Biomolecules Facility to other centers at Mayo Clinic.The facility brings together physicians, researchers, engineers and technicians to create and manufacture unique materials and devices to advance therapy for unmet patient needs.This is translational medicine: improving health by turning discoveries into new treatments.Potential therapies are first studied in the lab. Then, if proven safe and feasible, they move to clinical trials, and Dr. Greenberg helps make this happen. With her understanding of the science and regulatory requirements, she seeks to prevent wasted time and resources by helping Mayo innovators navigate the often-convoluted path to an approved new treatment.Dr. Greenberg is part of the Mayo Clinic Center for Regenerative Medicine. She coordinates with Mayo’s Center

Alexandra Greenberg, Ph.D.

for Clinical and Translational Science and Center for Excellence in Regulatory Science and Innovation, part of the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. By finding and casting the correct actors, Dr. Greenberg helps the centers function better and bring innovative care to patients faster.

Thu, Aug 31 9:37am · Novel Stem Cell Treatment Means New Lease on Life

As part of a pioneering clinical trial, Jared Ausnehmer had millions of stem cells injected into his heart to help treat a debilitating heart condition. That treatment has opened the door to renewed health for Jared.

Halloween is an especially meaningful day for Jared Ausnehmer and his family. On Oct. 31, 2011, Jared’s family saw a news story about a man who had had stem cells injected into his heart to reverse damage from a heart attack. Jared’s mom, Patty Ausnehmer, wondered if this type of treatment could help her son, who was born with hypoplastic left heart syndrome — a birth defect in which the left side of the heart is underdeveloped or nonexistent.

The news story kicked off a search for answers that led Jared and Patty to Mayo Clinic’s Rochester campus, where he participated in an innovative clinical trial. The trial paved the way for Jared to have successful heart surgery. As a result, Jared is no longer weighed down by his heart condition, and he’s returned to the athletic activities he enjoys.

“Mayo Clinic is an amazing place. They care, and they know what they’re doing,” Jared says. “I’m most grateful that I’m not sick anymore and everything went well. You can’t take that for granted.”

Search for something better
A rare congenital heart disease, hypoplastic left heart syndrome affects only about 1,000 newborns in the U.S. each year. Jared received a variety of treatments, including multiple surgeries during his first year of life and medications to improve his heart function. Still, by the time Jared reached his early 20s, his heart was enlarged and its neoaortic valve was leaking badly.

“I just didn’t feel well. I was tired all the time and was retaining a lot of fluid,” says Jared, who went from playing basketball and softball, and running track in the Special Olympics, to lying on the couch all day.

Eager for a new treatment option, Patty called the hospital that was mentioned on the news. Unfortunately, they weren’t doing stem cell therapy for Jared’s condition. But she didn’t stop there. The story spurred Patty to learn more about the possibility of stem cell therapy for hypoplastic left heart syndrome.

In the course of her research, Patty found Mayo Clinic’s Center for Regenerative Medicine and had a phone consult with Tim Nelson, M.D., Ph.D., a Mayo Clinic physician and researcher whose work focuses on congenital heart disease. Dr. Nelson told Patty that Mayo Clinic was starting stem cell therapy for infants with hypoplastic left heart syndrome but not for young adults like Jared.

“I explained our mission and desire to design such a trial in the future,” Dr. Nelson says.

Although treatment with stem cells wasn’t an option at that time, Jared and his family learned that through Mayo Clinic’s Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome, he could participate in another study and receive care from Mayo Clinic doctors with years of experience in treating the condition until a stem cell clinical trial became available.

Read the rest of the story on Sharing Mayo Clinic. 

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The Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) is a collaborative network of specialists bonded by the vision of delaying or preventing heart failure for individuals affected by congenital heart defects including HLHS. The specialized team is addressing the various aspects of these defects by using research and clinical strategies ranging from basic science to diagnostic imaging to regenerative therapies. To learn more or to participate in the research, email HLHS@mayo.edu and follow the HLHS program on FacebookTwitter and Instagram.

Thu, Aug 24 12:11pm · Regenerative Diabetes Conference on Islet Regeneration and Replacement: Sept. 29-30

Registration is now open for the Mayo Clinic Regenerative Diabetes International Conference on Islet Regeneration and Replacement. The conference will take place Sept. 29-30, 2017 in Rochester, Minn. Registration is free, but seating is limited.

The Mayo Clinic Regenerative Diabetes International Conference on Islet Regeneration and Replacement brings together academia and industry leaders from diverse areas of islet regenerative research.

The conference is designed for basic and translational researchers, clinicians, and representatives from funding and regulatory agencies.  More than 20 speakers will present on a range of topics on regenerative medicine and stem cell therapeutics for Diabetes Mellitus. See the agenda for a complete list of speakers and topics.

Mayo Clinic Regenerative Diabetes International Conference on Islet Regeneration and Replacement
Friday, Sept. 29, 1-6 p.m. CT
Saturday, Sept. 30, 8 a.m. – 4 p.m. CT

Mayo Clinic – Rochester, Minn
Gonda Building, Subway Level
Geffen Auditorium

View the agenda and register here.  For more information, contact the Mayo Clinic Center for Regenerative Medicine.

Thu, Aug 17 9:27am · New Start-Up on the Front Lines of the Fight Against Inherited Eye Disease

This story first appeared on the In the Loop blog.

When Alan Marmorstein, Ph.D., arrived on Mayo Clinic’s Rochester campus four years ago, he had a specific goal in mind: Find a way to counteract the vision loss that often comes with common and inherited eye diseases like macular degeneration and glaucoma.

The biggest break in that quest to date, the Rochester Post-Bulletin reports, came when Dr. Marmorstein and his lab team at Mayo Clinic developed a new process for growing retinal pigmented epithelium (RPE) cells, which are often used in eye-related research. According to the newspaper, the new and improved retinal cells, “perhaps created from a person’s own skin cells,” could replace the dead cells that cause macular degeneration. Researchers believe that transplanting these new RPE cells into the retina could restore vision to those affected by the condition.

To Dr. Marmorstein’s (and other researchers’) delight, these new cells, which are created from induced pluripotent stem cells, are proving to be “of better quality than the standard RPE cells” used in research.” And demand is growing, according to Twin Cities Business magazine. There’s just one catch. (Isn’t there always?) The process for making the new cells “is not trivial” and is “more expensive,” according to the P-B.

And so in 2015, Dr. Marmorstein launched LAgen Laboratories, a start-up company that focuses entirely on the “time-consuming,” “expensive” and “particular” process of growing the cells for use by scientists at academic research facilities around the world. Using the process he helped develop (and has since licensed from Mayo Clinic), Dr. Marmorstein and his small team at LAgen grow the cells in their “biologics manufacturing facility” in Rochester. When ready, researchers can order the cells “in flasks, in multi-well plates, and in other forms.”

“It’s painstaking to generate these cells, but they’re necessary to develop treatments for RPE-degenerative diseases such as macular degeneration, which affects as much as one-third of people older than 75,” Dr. Marmorstein recently told Mayo Clinic’s Alumni magazine.

And while the P-B notes that business is booming for LAgen, Dr. Marmorstein tells the paper his young company’s “ultimate goal is to treat macular degeneration.”

Getting there, he admits, won’t be easy (or quick). So for now, Dr. Marmorstein says he’s just happy to have the continued support of Mayo Clinic and the Rochester business community. “I find Rochester to be very supportive of start-ups,” he tells Alumni. “Mayo Clinic Ventures was encouraging and pointed me to local resources, including the Mayo Clinic Business Accelerator and RAEDI (Rochester Area Economic Development Inc.). One step led to another, and I connected with other entrepreneurs in the city who helped with aspects of business I wasn’t familiar with.”

You can read more about Dr. Marmorstein’s work to rid the world of inherited eye diseases here, here, and here. And check out Dr. Marmorstein’s recent video interview on requirements and procedures for clinical trial participation on the Macular News website, a service of the Macular Degeneration Foundation.

 

 

Thu, Aug 10 3:00pm · Researching the Use of Stem Cells for ALS - Nathan Staff, M.D, Ph.D.

Nathan Staff, M.D., Ph.D.

Nathan Staff, M.D, Ph.D., and his team are researching the potential of cell-based therapies to promote the healing response for patients with Amyotrophic lateral sclerosis, or ALS. A fatal neurodegenerative disease, ALS causes progressive paralysis and death in 2-5 years. Currently, no curative treatment exists for this devastating condition. While it is a rare disease, treatments for ALS may be translated to other more common neurodegenerative diseases such as Alzheimer disease and Parkinson disease.

Funding from Regenerative Medicine Minnesota, a state-wide initiative to improve the health of Minnesotans by advancing regenerative medicine research, education, industry and care delivery to patients, allowed Dr. Staff to initiate and conduct a Phase II study of mesenchymal stem cell therapy for ALS.

Learn more about Dr. Staff’s research:

 

 

Thu, Aug 3 9:51am · Persistence Powers Mayo Clinic's Approach to Adult-Derived Stem Cell Therapies

This story was previously published in Mayo Clinic Magazine.

Allan B. Dietz, Ph.D., never intended to be a scientist.

His plan was to be a farmer, just like his father, grandfather and all the other Dietzes he knew.

“I was going to be a farmer at first. Then I was going to be a veterinarian because that’s what farm kids who like science did,” Dr. Dietz says.

But the rural Iowa boy’s plans quickly changed when he lost interest in agriculture right about the time he entered the doctorate program for genetics in the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University.

“I liked the science so much I decided to just do the science,” he said.

Humbled Daily

Dr. Dietz joined Mayo Clinic in 1996 and has been a driving force behind the research into medical treatments using cell-based technologies, including adult-derived stem cells known as mesenchymal stem cells. Dr. Dietz is the director of the Human Cell Therapy Laboratory. The lab develops cellular therapies to treat a variety of conditions.

There are versions of the lab at all three Mayo Clinic campuses with support from the Center for Regenerative Medicine. When a physician-scientist explores if stem cells or other cellular therapies could be an option for a patient’s disease or condition, he or she works with Dr. Dietz’s team to develop the protocol and cellular product.

This readily available expert support reduces the time it takes to move research from the initial concept to the actual creation of a product that can be tested.

“This is not a solo effort,” Dr. Dietz says. “I really believe that I have the most caring, hardworking team of physicians, scientists and support staff ever assembled. I am humbled daily by the opportunity to work with them.”

Without the lab, physicians could spend years gaining the expertise in stem cells as well as necessary Food and Drug Administration approvals to move into clinical trials. With assistance from Dr. Dietz’s lab, that time can be cut significantly — to less than a year in some cases.

“Dr. Dietz provided invaluable leadership in guiding us through the very complicated path of obtaining FDA approval for our first stem cell trials. Without Dr. Dietz, these trials would not have been possible,” says neurologist Anthony J. Windebank, M.D. “He has endless enthusiasm and a very practical approach to getting things done efficiently.”

That practical approach began when Dr. Dietz was a boy.

“My ability to solve problems and my work ethic come from growing up on a farm,” Dr. Dietz says. “On a farm, you’re almost always limited in resources. So your first response to any problem is, ‘How can I solve it with the things I have?'”

Finding a Powerful Tool

At the time he was recruited to work at Mayo Clinic in Rochester, Minnesota, there was no regenerative medicine field as it is thought of today.

The laboratory’s history is rooted in transfusion medicine — the act of collecting and testing blood to be given to patients at Mayo Clinic. In the history of blood banking, researchers found it to be a powerful tool for healing. “When you differentiate blood, cut it into different pieces, such as platelets, packed red blood cells or plasma, you have more treatment options,” explains Dr. Dietz.

“The body has tissues with powerful healing properties, and we just need to figure out how to tease them out.”

Recognizing the potential, Mayo Clinic sought a scientist who could take this research to the next logical extension and explore other opportunities for treatments created from human cells.

The field was so new and unexplored that Mayo Clinic did not even know how to advertise the position, but as luck would have it, there were a few researchers in transfusion medicine who knew a scientist known for taking on challenging puzzles. That scientist was Dr. Dietz.

The Next Step

Dr. Dietz started his work on cancer vaccines with the Mayo Clinic Cancer Center, and after developing one approach, he spoke to his division leader at the time, S. Breanndan Moore, M.D., to find out what he thought his next project should be.

“Dr. Moore said, ‘Why are you asking me? You’ll know,'” Dr. Dietz recalls.

As it turns out, he did.

Dr. Dietz was inspired by a single case study reported in literature of mesenchymal stem cells dramatically reducing one patient’s inflammatory response to graft-versus-host disease, which is often fatal.

“That was all I needed as a flag to go: ‘That’s the new thing we’re going to work on!'”

What came next was a six-year odyssey to do all the background scientific work to develop these cells as a powerful drug platform. Collaborating with Dr. Windebank, who was working with patients with amyotrophic lateral sclerosis (ALS) — also known as Lou Gehrig’s disease — Dr. Dietz realized that these cells could be a “last great hope” for these patients.

A New Inspiration

But it was not until the disease hit close to home that Dr. Dietz really understood what these patients and their families were facing.

As his team worked toward a clinical trial, Dr. Dietz was called into the office of Dr. Moore.

“He was a great practical joker, so he sat me down and asked, ‘How’s that ALS trial?’ and after being reassured that it was going well, he asked, ‘Do you think I’ll be eligible for it?’ At first, I thought he was joking, but he had been diagnosed recently with ALS.”

Dr. Dietz and his team applied to do a one patient trial so that they could bring the treatment more quickly to their friend and colleague.

“He didn’t want us to do anything to compromise the integrity of what we were doing, but we framed it as fast as we possibly could,” Dr. Dietz says.

The day they got the permission to run the single-patient trial, Dr. Dietz called Dr. Moore to share the good news. It was too late.

“He had been moved to hospice that morning,” Dr. Dietz says, his voice cracking. “So, Breanndan missed it.”

Devastated by the loss of his mentor, colleague and friend in 2009, Dr. Dietz and his team continued to plug away at the problem. This radical approach to treating patients rarely found support by traditional funding sources.

A Gigantic Unmet Need

While the Mayo Clinic Department of Laboratory Medicine and Pathology and the Center for Regenerative Medicine provided financial help for the Human Cell Therapy Laboratory, critical funding has come from benefactors. Dr. Dietz and the lab have done the heavy lifting needed to develop multiple cell-based treatments. This development work is amplified as this new important class of cellular drugs gets into the hands of physicians. The combination of the Human Cell Therapy Laboratory developing these drugs and clinical experts using these drugs supported by like-minded donors is a powerful combination.

“There isn’t anybody who’s not touched by one of these terrible diseases, and we started out purposely picking really tough ones like brain cancer, ALS, multiple system atrophy and wounds that won’t heal, because there is nothing else for these patients,” Dr. Dietz says. “It is a gigantic unmet need.”

And Dr. Dietz’s stubborn work ethic propels him to meet those needs for patients.

“Science is very much like a farm: an endless amount of work and a new flavor of problems every day,” Dr. Dietz says. “It is up to us to figure it out.”

Tue, Jun 27 12:26am · Regenerative Cardiac Synchronization – Satsuki Yamada, M.D., Ph.D.

A heart attack occurs when the flow of blood to the heart is blocked, most often by a build-up of fat, cholesterol and other substances, which form a plaque in the arteries that feed the heart (coronary arteries). The interrupted blood flow can damage or destroy part of the heart muscle. Satsuki Yamada, M.D., Ph.D., a recent recipient of a Regenerative Medicine Minnesota Translational Research Grant, is investigating the use of patient’s own stem cells as a new therapy to help reestablish and maintain a synchronized pumping motion in the infarcted heart.

Dr. Yamada is an assistant professor of medicine at Mayo Clinic. Her study seeks to develop a regenerative therapy to correct disrupted wall motion (“cardiac dyssynchrony”) after a heart attack. Under conditions replicating patient management of this resilient disorder, the safety and efficacy of a new class of patient-derived stem cells delivered into diseased heart regions will be tested by a multidisciplinary team. Successful outcome will provide the foundation for first-in-human studies targeting heart muscle synchronization in refractory heart failure.

Learn more about Dr. Yamada’s research:

Fri, May 19 10:35am · Immune-Building Stem Cell Research

Cesar A. Keller, M.D.

In the 1970s, when Cesar A. Keller, M.D., started his career in pulmonology, lung transplantation was widely considered science fiction. Now, lung transplantation is a lifesaving option for thousands of people every year, but it’s not perfect, Dr. Keller says. For adults, the five-year survival rate is about 55 percent, according to 2008–2015 lung transplant data from the Department of Health and Human Services. With the help of philanthropic support, Dr. Keller and colleagues in the Mayo Clinic Center for Regenerative Medicine are trying to solve the most lethal imperfection of lung transplantation, a syndrome called chronic organ rejection.

Moving From Rejection to Acceptance
Chronic rejection is considerably more common in lung transplantation than in other solid organ transplants. This is most likely due to environmental factors, which “the lungs are exposed to continuously, with every breath a patient takes,” Dr. Keller explains.

To solve that challenge, Dr. Keller and his colleagues are using tools that are today’s version of science fiction becoming science fact: stem cells and regenerative medicine. Stem cells have the ability to repair damaged cells, transform into almost any cell the body needs and temper the immune system. So, Dr. Keller’s team launched an initial clinical study to evaluate safety and dose considerations of stem cell use in lung transplant patients who have chronic organ rejection. Researchers also gathered data on whether the treatment may have potential for improving lung function or slowing the progressive decline in function that occurs with chronic organ rejection.

The study used bone marrow-derived stem cells, which were infused through an IV and circulated to the lungs. The lungs “trap all of the stem cells,” Dr. Keller says. His team is preparing for a larger clinical study that will be based on the initial study results. “It took us seven years from our concept to delivering stem cells to the first patient,” he says.
“It’s going to take at least another seven or eight years to see if this is successful.”

DEVELOPING LUNG RESTORATION CAPABILITIES 

This research and other activities in the Center for Regenerative Medicine will be extended by another new technology that is coming to the Florida campus. In 2016, Mayo Clinic and United Therapeutics broke ground on a lung restoration center that could more than double the number of donor lungs viable for transplantation in the United States. United Therapeutics is working to improve donor lungs and make them suitable for transplantation
using “ex vivo lung perfusion technology.” The technology stores lungs in a specialized chamber and treats them with solutions and gases that can reverse lung injury and remove excess fluids.

Dr. Keller says the technology, which preserves lungs when they are outside the body, can be used to research the benefits of delivering stem cells to lungs before they are transplanted into a person. That strategy may help reduce immune system responses after the lungs are transplanted. “It was literally all science fiction when I began,” Dr. Keller says. “It’s interesting to think about where the field was when I started and to see these concepts become things we can apply.”

 

 

 

 

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