Mayo Clinic physicians and researchers are using stem cells and other regenerative therapies to help athletes get back in the game faster, avoid or delay surgery, or heal faster or better after surgery. Recovering from injury is challenging for athletes at any level, but innovative new therapies use stem cells and other biological tools to help athletes regenerate damaged tissue to recover from injuries faster, slow or reverse the effects of overuse in joints, and extend their playing careers. These same approaches may also be able to save and transform the lives of people of all walks of life who suffer from serious diseases or injury.
“We’ve been doing regenerative medicine in the Sports Medicine Center at Mayo Clinic for nearly 15 years,” said Dr. Jonathan Finnoff, medical director of Mayo Clinic Sports Medicine at Mayo Clinic Square in downtown Minneapolis. As the technology has advanced, the field has risen in importance to Mayo, which established its Center for Regenerative Medicine in Rochester in 2011. “This is a big deal for Mayo Clinic,” Dr. Finnoff said.
Click here to read the Greater MSP’s profile on regenerative sports medicine at Mayo Clinic.
Shane Shapiro, M.D., is dedicated to advancing the science of orthopedics and regenerative medicine through research. He is assistant professor of orthopedic surgery and program director for the Regenerative Medicine Therapeutic Suites, Mayo Center for Regenerative Medicine.
In the video below, Dr. Shapiro discusses the results of his randomized controlled trial of bone marrow aspiration and concentration for knee osteoarthritis — early results of this clinical trial were published in the American Journal of Sports Medicine.
The Mayo Clinic Center for Regenerative Medicine is a co-organizer of the 2018 World Stem Cell Summit. More than 1,000 attendees are expected at the 13th annual event Jan. 22-26 in Miami, Florida. Researchers and clinical experts from Mayo Clinic will participate in presentations and panel discussions highlighting advances in discovery science, promising clinical trials and available therapies. Topics to be covered include biomedical ethics, bioprinting, and regenerative medicine at the point of care.
The Mayo Clinic featured presenters include:
Richard Hayden, M.D.
Dr. Hayden is a head and neck surgeon and director of education for the Center for Regenerative Medicine. Dr. Hayden will participate in the panel discussions: “Mistakes, Malpractice and Institutional Failures: The Real Barriers to Therapeutic Progress.”
David Lott, M.D.
Dr. Lott is a head and neck surgeon and associate director for the Center for Regenerative Medicine in Arizona. He directs the Department of Otolaryngology Head & Neck Surgery/Audiology, Voice Program. He also directs the Head & Neck Regeneration Laboratory where he and his team research transplantation techniques, tissue engineering, and restoring function of the larynx. Dr. Lott will participate in the panel discussion: “Feats of Wonder: Updates on Bioprinting and Body-on-a-Chip.”
Zubin Master, Ph.D.
Dr. Master is an associate consultant in the Biomedical Ethics Research Program at Mayo Clinic. He will participate in two panel discussions: “Navigating the Legal Minefield – What Clinicians and Patients Need to Know Before Undertaking a Cell-Based Therapy Treatment” and “Ethical Considerations: Editing the Human Genome.”
Shane Shapiro, M.D.
Dr. Shapiro is the program director for the Regenerative Medicine Therapeutic Suites in Florida. He is a consultant in the Department of Orthopedic Surgery. Dr. Shapiro was instrumental in establishing the outpatient regenerative medicine therapeutic suites as a dedicated space for clinicians to integrate regenerative technologies into patient care. He will participate in two panel discussions: “Navigating the Legal Minefield – What Clinicians and Patients Need to Know Before Undertaking a Cell-Based Therapy Treatment” and “Stem Cells and Regenerative Medicine at the Point of Care.”
Wenchun Qu, M.D., Ph.D.
Dr. Qu is director of the Regenerative Pain Medicine Practice at Mayo Clinic. He is a consultant with the Department of Physical Medicine and Rehabilitation, the Department of Anesthesiology Division of Pain Medicine, and the Spine Center at Mayo Clinic. Dr. Qu’s research interests include stem cell therapies for degenerative conditions of the spine and musculoskeletal system. He will participate in two panel discussions: “China’s Impact on the World of Regenerative Medicine” and “Stem Cells and Regenerative Medicine at the Point of Care.”
Seven Mayo Clinic investigators were selected to receive 2018 Regenerative Medicine Minnesota research grants. The grants are awarded to investigators in the areas of discovery science, translational research and clinical trials. The grants are effective for a two year period.
Mayo Clinic awardees include:
Terry Burns, M.D., Ph.D. Dr. Burns, a neurosurgeon, is developing regenerative strategies to optimize neurological function and quality of life for patients with brain tumors, neurological injuries and neurodegenerative diseases. He is leading efforts to understand and overcome the challenges of clinical translation for neuroregenerative therapies. Dr. Burns’ research grant proposes to study the safety and mechanisms of senolytic therapy for central nervous system rejuvenation.
Mohamad Bydon, M.D. Dr. Bydon is a neurosurgeon who is fellowship-trained in complex spinal surgery and spinal oncology. He specializes in minimally invasive spine surgery and spine oncology and serves as principal investigator of the Mayo Clinic Neuro-Informatics Laboratory. The laboratory established this clinical trial with multi-disciplinary colleagues in Neurology, Physical Medicine and Rehabilitation, Transfusion Medicine and others. The goal of the trial is to investigate whether adipose-derived (fat tissue-derived) mesenchymal stem cells can be safely administered into the cerebrospinal fluid of patients with traumatic spinal cord injury and to study the impact of the cells on functional improvement, activities of daily living, and quality of life.
Ping Chen, Ph.D. Dr. Chen is an assistant professor and research associate in Molecular Pharmacology and Experimental Therapeutics. The major challenge in treating obesity is not just losing weight, but preventing weight from coming back. Her proposal examines a new treatment strategy of using a gene transfer therapy to safely target brain mechanisms that control hunger and energy output.
Aaron Krych, M.D. Dr. Krych is a professor of orthopedics and a consultant in the Department of Orthopedic Surgery. His research project proposes to test the initial safety and feasibility of RECLAIM, a single stage cartilage repair technique using the patient’s own cartilage cells and allogeneic mesenchymal stem cells. The study will assess patient’s improvement in pain and function following the procedure, while actively monitoring safety and adverse events.
Joseph Lillegard, M.D., Ph.D.
Dr. Lillegard is a supplemental consultant at Mayo Clinic and a pediatric general and thoracic surgeon at Children’s Minnesota. He is researching gene therapy to fight inborn errors of metabolism of the liver, primarily Hereditary Tyrosinemia Type 1 (HT1), a metabolic disorder caused by an enzyme deficiency. With the Regenerative Medicine Minnesota award, he is investigating the safety and efficacy of direct therapeutic lentiviral vector administration to large animal models of disease.
Alexander Revzin, Ph.D. Dr. Revzin is a professor of biomedical engineering at Mayo Clinic. The goal of his project is to develop microcapsules that could be used as cell carriers during differentiation of stem cells into pancreatic islets. These same capsules may also be useful as vehicles for islet transplantation. This technology will enable better scale-up of islet production from stem cells, may result in cost reduction, and may also alleviate problems associated with immune rejection of transplanted islets.
Jennifer Westendorf, Ph.D. Dr. Westendorf is the Margaret Amini Professor of Orthopedic Regenerative Medicine Research and a consultant in the Departments of Orthopedic Surgery and Biochemistry and Molecular Biology. Her research project will determine how Girk2/3 potassium channels contribute to cartilage formation and repair in the setting of osteoarthritis.
About Regenerative Medicine
Regenerative medicine focuses on the body’s natural ability to repair, replace, and regenerate damaged or aging tissues, and to restore functionality. Physicians and scientists are using native and bioengineered cells, assistive devices, and engineering platforms to develop new treatments with the potential to fully heal the underlying causes of diseases, rather than only manage disease symptoms.
About Regenerative Medicine Minnesota
Regenerative Medicine Minnesota is a joint venture between the University of Minnesota and Mayo Clinic, and funded by the Minnesota Legislature, with the goal of distributing millions of dollars to advance regenerative medicine in the state through research, education, healthcare, and business. The program, which was funded during the 2014 legislative session for ten years, is in its fourth year of operation.
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.”
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.”
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.
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.
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., 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
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.
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 Facebook, Twitter and Instagram.
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
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-Bulletinreports, 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 toTwin 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.