People, on average, are living longer than ever before. In part, this is due to medical advances that have made it possible to save more people from life-threatening diseases, injuries and congenital conditions. But as people live longer, they’re more likely to acquire chronic diseases or develop age-related conditions.
After the onset of most chronic diseases or injuries, the damage is there to stay — consider scarring of heart tissue from a heart attack, beta cell dysfunction in diabetes or a spinal cord injury from an accident. Symptoms can be managed, oftentimes with good success, but the underlying tissue or organ damage remains unhealed and can cause complications over time.
The Mayo Clinic Center for Regenerative Medicine was established to develop new clinical applications that address the unmet needs of these patients and to harness the capabilities of Mayo across disciplines. Jay Smith, M.D., vice-chair of Mayo Clinic Physical Medicine and Rehabilitation in Minnesota, talks about the center, the field of regenerative medicine, and takes viewer calls on KSMQ Health Connections.
In the body, repair is constant process. So it’s a good thing the body has a Star Trek-like replicator in the mesenchymal stem cell. These act as the raw material for future muscles, cartilage, or bone cells, to name a few. But scientists at Mayo report that if the ship isn’t healthy, the replicator may suffer too.
Researcher Lilach Lerman, M.D., Ph.D., led the team that examined how mesenchymal stem cells act in an animal model of metabolic syndrome —a set of conditions that increase risk for cardiovascular diseases and diabetes. They report that stem cells in pigs with metabolic syndrome are shifted down a pathway that leads to stasis instead of repair, as compared to lean pigs.
Stasis for a cell is a state called senescence. These senescent cells hover between life and death, spewing out inflammatory molecules to disrupt the function of cells in their vicinity. It’s not a good condition, but it may be a necessary one: If a cell is headed down the road toward cancer, it may receive instructions to die, but if it can’t then it may enter this senescent state.
Dr. Lerman and team had previously observed that pigs with metabolic syndrome had fewer functional mesenchymal stem cells and more senescent stem cells than lean pigs. In their recent publication in the journal Cell Transplantation, they expand on those findings and show one way that metabolic syndrome might affect the stem cells.
It goes like this: biological effects of high blood pressure, abnormal cholesterol or triglycerides, excessive blood sugar, and/or excess body weight around the waist shift the directions cells are given and send them down the road of senescence and the senescence associated disruption that comes with it. The directions, the researchers report, come in the form of short bits of RNA called microRNA. These short fragments interfere with the ability of messenger RNA to take instructions received from the DNA to a ribosome so protein a can be made.
In lean and metabolic syndrome animals, the researchers found differences in 10 microRNAs that, collectively, are linked with 35 senescence-associated genes.
Next, the researchers will explore these genes and the molecules that regulate these pathways in greater detail, in the hope of improving stem cell function for humans managing a chronic disease state.
And to help move us into the era of Star Trek, the team hopes their information improve the use of stem cells gathered from the body as a regenerative medicine tool. Ship or body, replicator or mesenchymal stem cell, understanding how to keep the repair system in good working order means a smoother ride for all.
This article originally appeared in Mayo Clinic’s research magazine, Discovery’s Edge.
For years, Rick Amatuzio lived with severe back pain that kept him from an active life. But advanced diagnostic tests and regenerative medicine therapy at Mayo Clinic ultimately led to a complete recovery.
A typical weekend for Rick Amatuzio involves playing two rounds of golf, riding his motorcycle and mountain biking. But less than two years ago, the active motocross champion couldn’t get out of bed or stand up straight. Debilitating back pain kept him from doing many of the activities he’d once enjoyed.
“I can recall crawling to the bathtub many mornings on my hands and knees in an attempt to loosen my body for the upcoming day,” Rick says. “You feel helpless, emptiness, and like there’s nowhere to turn for help to improve the situation.”
Rick finally found the help he needed when he sought care at Mayo Clinic in 2017. Wenchun Qu, M.D., Ph.D., a specialist in physical medicine and rehabilitation and pain medicine, offered Rick a treatment that involved injecting stem cells into his spine. It worked. Now Rick’s pain is gone.
“Dr. Qu is one of the best doctors I’ve ever seen,” Rick says. “He didn’t make promises, yet he gave me a lot of hope.”
Rick can trace his back issues to 10 years ago, when the Duluth, Minnesota, resident had spinal fusion surgery to correct a spine condition known as spondylosis. Two years after that surgery, Rick began noticing a dull ache in his lower back that got progressively worse each year until he had a pain level of 7 out of 10 for most of the day.
“I was getting epidural steroid shots, which would help for a month or two, and then the problem would return,” Rick says. “I was taking six or eight Tylenol a day.”
When the pain kept him from getting more than an hour of sleep at night, Rick’s local neurosurgeon, who had performed the spinal fusion, recommended he go to Mayo Clinic to pursue regenerative medicine therapy.
During his first consult with Dr. Qu in May 2017, Rick was diagnosed with a spine disorder known as adjacent segment disease. The disease had developed as a result of his spinal fusion.
I was getting epidural steroid shots, which would help for a month or two, and then the problem would return. I was taking six or eight Tylenol a day.
“Adjacent segment disease is when you have a fusion of two vertebrae, and the next level of vertebrae have to move more to compensate, which causes those discs to wear out,” Dr. Qu says. “Imaging studies showed he had quite active disease in the discs below the fused discs.”
The next step was to do a test called a provocative discography. It could determine whether the worn discs were causing Rick’s pain. The test involved injecting contrast dye in the discs to put pressure on them and reproduce the pain he’d been feeling. Test results confirmed the pain was coming from Rick’s degenerated discs.
To treat Rick’s condition, Dr. Qu recommended an approach that used regenerative medicine. Unlike traditional treatment for adjacent segment disease that destroy the discs by burning or fusing them, Dr. Qu would treat the disc degeneration with therapy to reduce the inflammation that was responsible for Rick’s pain.
“Stem cells have growth factors which activate the dormant cells indigenous to the disc and restore the health of the disc by reducing inflammation,” Dr. Qu says. “If you reduce inflammation, you reduce pain.”
“It takes about two months, or even longer, to see the treatment effect, and I have seen low-level inflammatory responses in between,” he says.
But throughout that period, Rick felt the support of his Mayo Clinic care team. “Dr. Qu and his team stood with me and helped me through the process,” he says. “They would call or email frequently to see how I was doing.”
I am extremely grateful for Dr. Qu and Mayo Clinic. They have given me my life back.
By the time he celebrated his 44th birthday in March, Rick was feeling much better. Since then, he’s lost 30 pounds and can now carry his golf bag for 36 holes without pain. He says it’s the best he’s felt in 12 years.
“I wake up in the morning, and I can stand up straight easily. The burning pain in my back and the back of my legs is gone. I can sleep through the night. I can go out with my friends without discomfort. I work out every morning. I can go mountain biking,” Rick says. “I am extremely grateful for Dr. Qu and Mayo Clinic. They have given me my life back. Every day is a blessing that I can do the activities I enjoy doing.”
Hear from keynote speakers on trends in clinical application, discovery science, regulatory science, cGMP manufacturing and quality assurance, and clinical trials. Sessions planned for the three-day symposium include:
Regenerative Medicine Breakthroughs
Clinical Trials & Clinical Experience
Future of Regenerative Medicine
Accelerating Therapies to Application
Enterprise Translational Capabilities
Interactive Training and Education sessions
The latest symposium agenda, along with the event details, can be found on the symposium website
Mayo Clinic will nearly double the size of its Phoenix campus to meet growing patient demand and further position Mayo Clinic in Arizona as a premier destination medical center. The development of regenerative medicine therapies and the buildout of regenerative medicine suites are integrated into the $648 million expansion plan.
As part of the project, the model used for the Regenerative Medicine Therapeutic Suites at Mayo Clinic in Florida will be expanded to the Arizona campus. The model, which integrated patient care with laboratory functions, serves both patients and clinicians, providing a place for multidisciplinary teams to expand current projects in order to deliver individualized regenerative therapies and procedures to patients.
Read more about the five-year “Arizona Forward” project, including more highlights of the expansion, on the Mayo Clinic News Network.
Millions of Americans have chronic kidney disease. Hundreds of thousands will progress to end stage kidney disease requiring either dialysis or kidney transplant. But research is underway to keep people from reaching that point.
“Our goal is to take a look at how we can repair the diabetic kidney in terms of delaying the rate of progression of kidney failure,” says LaTonya Hickson, M.D., a Mayo Clinic nephrologist.
Dr. Hickson is part of the research team looking at using stem cells to help regenerate failing kidneys.
“We take these cells from our abdominal fat and we can inject them back into the body for them to do good,” says Dr. Hickson. “They basically tell the kidney or other organ systems that are impaired to wake up and get back to work and help heal that organ system.”
While there’s a lot more research ahead, Dr. Hickson is excited about the possibilities.
Dr. Lightner was recently honored with the Sherman Emerging Leader Prize for making impressive contributions early in her career and demonstrating strong potential to make an even greater impact in the future. (Photo courtesy of Dark Spark Media.)
Volunteering for a reading program at a children’s hospital led to a career change for Amy Lightner, M.D. As a Stanford University undergraduate, she met a cardiac surgeon who turned her interest to medicine.
“I got to see how medicine and surgical intervention could change a child’s life forever,” says Dr. Lightner. “The research, in parallel, changed lives of thousands, and this combination of clinical practice and translational research was inspiring.”
Today Dr. Lightner is a Mayo Clinic colorectal surgeon, practicing minimally invasive surgical approaches and researching regenerative cellular therapies for some of the most difficult complications of inflammatory bowel disease (IBD). She is recognized as an emerging leader for her achievements in improving surgical outcomes for patients.
Dr. Lightner completed her general surgery residency and two years of full-time research studying stem cell biology in a liver regeneration and immunology laboratory. While she found liver transplantation fascinating, it was while she was finishing her clinical training she turned her focus to IBD and a career in colorectal surgery. IBD is an umbrella term used to describe disorders that involve chronic inflammation of the digestive tract, including ulcerative colitis and Crohn’s disease.
“I would see young patients suffering from chronic bowl disease coming to terms with suffering for the rest of their lives without a known cure,” says Dr. Lightner. “Surgery treated the symptoms but not the disease, and I thought we could do so much better than the current treatment options — we needed to find out how to treat the underlying disease.”
Dr. Lightner immersed herself in a Mayo Clinic fellowship for complex clinical care and stem cell research to treat perianal Crohn’s disease. It was during this time she started to see a connection to stem cells and the therapy for IBD. “This was the time that regenerative medicine was taking off at Mayo and becoming an institutional priority,” says Dr. Lightner. “The timing was perfect.”
For patients with ulcerative colitis, a proctocolectomy, or removal of the colon and rectum, is often a last resort. After a proctocolectomy, a J-pouch surgery is performed to create an internal pouch, eliminating the need for a permanent ostomy bag. However, in about 10 to 15 percent of patients the pouch will fail and they will need a permanent ostomy.
Dr. Lightner offers these patients an alternative. She is among a small group of surgeons across the country that is skilled at pouch reconstruction – giving patients a chance at an ostomy-free life.
While an innovative physician who is an expert at reconstructive pouch surgery, Dr. Lightner wants to see fewer IBD surgeries. She is currently researching innovative cellular, non-surgical therapies.
“Regenerative medicine with novel cellular and acellular therapies is the future of medicine,” says Dr. Lightner. “I want to change the way we think of treating IBD to focus on repair derived from our own cells.”
After seeing initial success in treating Crohn’s fistulas with adipose or bone marrow derived mesenchymal stem cells from healthy donors, Dr. Lightner is initiating a Phase 1 trial to explore a novel regenerative acellular therapy. The trial will be the first of its kind in perianal fistula, which affects approximately 25 percent of people with Crohn’s disease.
Translation into Practice Platforms Dr. Lightner is the enterprise medical director for the Translation into Practice Platforms (TIPPs) for the Center for Regenerative Medicine. The platform accelerates regenerative medicine clinical trials and advancements into clinical practice. Teams provide help with protocol design and writing, and support in communicating with the U.S. Food and Drug Administration.
Unique Laboratory Dr. Lightner’s research space is best described as a regenerative medicine surgical lab. This all-encompassing lab is working on optimizing regenerative products like extracellular vesicles and engineered mesenchymal stem cells. The work in the lab can be applied to other disease states, allowing these products to cross disciplines. The goal is to bring multiple investigators together, and find novel regenerative therapies for the treatment of multiple diseases.
The Mayo Clinic Symposium on Regenerative Medicine and Surgery will be held Nov. 29 – Dec. 1, 2018 at the Westin Kierland Resort in Scottsdale, AZ. Early-bird registration, which runs through Monday, Oct. 15, provides a savings of $100 off the conference fee. Register today.
The event will feature presentations on the latest advancements in regenerative medicine and surgery and will provide networking opportunities to those interested in regenerative medicine therapies and techniques. Learn more about the symposium, including keynote speakers, on the Center for Regenerative Medicine blog.