Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.


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2 days ago · Evolution of cardiac regeneration

large group of Mayo staff wearing red for heart disease awareness, posed on grass in sunshine
Wearing red for heart disease awareness is one thing all staff can do each year. More specific efforts are underway throughout Mayo Clinic research to find better ways to prevent and treat heart disease.

February is American Heart Month, a time to acknowledge advancements in a new generation of care. This year focus is placed on repairing damaged heart tissue and restoring heart function after a heart attack. The Mayo Clinic Center for Regenerative Medicine is leading research into cardiac regeneration.

Accounting for nearly 20 million of all deaths, heart disease is the leading cause of death worldwide. Currently, there is no way to replace muscle that has died after a heart attack as damage is often irreversible. Mayo Clinic researchers and clinicians are seeking to create innovative and more affordable and accessible cardiac regenerative therapies to restore heart muscle.  

Atta Behfar, M.D., Ph.D.

“Cell therapy has pioneered our ability to drive regenerative medicine forward,” says Atta Behfar, M.D., Ph.D., director, Mayo Clinic Van Cleve Cardiac Regenerative Medicine Program in the Center for Regenerative Medicine. “In order to be impactful in the next decade, cardiac regeneration efforts need to overcome current hurdles through innovation and development of new technologies that are both fiscally and logistically realistic.”

With the clinical experience accumulated in cardiovascular regeneration both at Mayo Clinic and globally, we now know that a tailored approach will likely provide the best outcomes. For a heart attack and stroke, which require urgent care, off-the-shelf cell-independent technologies that can be stored right at the bedside may be most effective. In contrast, for more chronic conditions like heart failure where a sustained regenerative impulse is required, cellular or gene-based therapies may provide a more robust end result. As the regenerative toolkit continues to grow, with new modalities to deliver restoring cues to the heart, so will our aptitude in offering new solutions to patients in need.

Michael Sabbah, M.D.

“Cell-based technologies have historically been poorly compatible with acute syndromes due to the emergent need for care,” says Michael Sabbah, M.D, Mayo Clinic cardiologist and researcher in the Mayo Clinic Van Cleve Cardiac Regenerative Medicine Program. Establishment of a room temperature-stable product that can be left on the shelf in a surgical or procedure room would allow the use of regenerative therapies at the point of care following stent implantation.”

A case in point, established in the Center for Regenerative Medicine, is the use of regenerative vesicles, termed exosomes which are the active ingredient of regeneration. Exosomes are packages of signaling molecules that act as communication links between cells in the regenerative healing process. They are like an envelope with instructions for healing that one cell mails to another. They can modify the immune response and facilitate blood vessel growth. This technological platform is now under active investigation at Mayo Clinic to evaluate its ability to protect the heart against injury in heart attack.

“In the laboratory, employment of exosomes has been successful,” says Dr. Sabbah. “Our goal is to leverage what we have learned to establish new tools to treat patients with acute cardiovascular syndromes, who currently suffer from devastating and long-lasting deficits. By utilizing a cell-independent platform, our ultimate goals is to develop regenerative technologies that may be employed by providers in a broad array of clinical areas, unencumbered by logistical hurdles that are sometimes seen with other regenerative approaches.”

Although the study and use of exosomes has progressed in the lab, researchers acknowledge that this is simply one example of the type of technological advance poised to broaden the scope of cardiac regeneration. Through the optimization of biologics-based science, researchers in the Mayo Clinic Van Cleve Cardiac Regenerative Medicine Program are expected to start clinical testing later this year.

“Cardiac regeneration has historically paved the way forward in establishing novel biologics-based platforms. Our hope is that as new approaches to restore heart function are implemented, they will inspire use of similar principles across medical and surgical specialties,” says Dr. Behfar. “In order to ensure that all patients receive the highest standard of care, we must utilize the discovery process not just as a paradigm to achieve translational successes, but even more importantly as a modality to break socioeconomic divides and improve access to care.”


This story first appeared on the Center for Regenerative Medicine blog.

Thu, Feb 20 6:00am · Restoring function with larynx transplantation

diagram of airway, larynx, trachea, vocal cords

Mayo Clinic has launched a first of its kind regenerative transplant program aimed at restoring function for people who need their larynx, or voice box, removed.

In the United States about 60,000 people are living without a larynx, due to disease or trauma. The larynx is a segment of the respiratory tract located in the neck responsible for protecting the airway, swallowing, and producing speech.

After a laryngectomy, the procedure in which the larynx is removed, the patient must breathe through an opening in their neck and communicate by using a machine or a special prosthesis implanted into the throat. Currently, there is no traditional reconstructive option that can restore all vital laryngeal functions.

“A laryngectomy severely alters quality of life. The ability to smell, taste, breathe, swallow and speak are all affected,” says David Lott, M.D., a laryngeal surgeon, associate director of the Center for Regenerative Medicine, and surgical director of the Larynx and Trachea Transplantation Program at Mayo Clinic in Arizona. “When the organ is damaged or removed due to disease, patients quickly realize how large of a role it played in their everyday lives.”

David Lott, M.D.

To help improve quality of life for these patients, Dr. Lott and his team have created the Larynx and Trachea Transplantation Program. They established a unique set of protocols which were approved by the United Network for Organ Sharing (UNOS) about a year and a half ago. UNOS regulates and manages the nation’s organ transplant system. Dr. Lott and his team have approval to perform two transplants per year over each of the next five years. The Larynx and Trachea Transplantation Program is the first UNOS-approved program of its kind.

“The larynx is a machine,” says Dr. Lott. “The larynx opens, closes and elevates; there is significant movement within the organ.”

Image showing schematic of larynx transplant
Representation of larynx transplant

In addition, the larynx contains muscle, tissue, fat, cartilage and bone, which makes for a complex immune environment. These factors can make the larynx much more complicated to transplant than other organs.

The transplantation itself is like putting together a puzzle. Once the donor larynx is ready for implantation, dozens of blood vessels, nerves and other structures must be reconnected. A successful larynx transplant would allow a patient to breathe through their mouth, swallow normally, and produce a human-sounding voice.

D. Eric Steidley, M.D.

“Larynx transplant provides the hope to improve quality of life for patients suffering the effects of severe laryngeal disease or tracheal injury,” says D. Eric Steidley, M.D., medical director of the Larynx and Trachea Transplantation Program. “We’re giving possibilities to patients who don’t have treatment options. It is a very exciting time for us to be in this field.”


This article was originally published on the Mayo Clinic Center for Regenerative Medicine blog.

Read a related story describing additional research from Dr. Lott’s team on building a new larynx out of a person’s own tissue.

See Dr. Lott’s related research publications on PubMed.

Mon, Feb 10 6:00am · Regenerative product could provide new option for women with mesh exposure following pelvic reconstructive surgery

medical illustration of vaginal prolapse

Research is advancing a regenerative solution for a quality of life-limiting complication of mesh-based surgical repairs for stress urinary incontinence and pelvic organ prolapse in women. While mesh-based surgical treatments are durable and provide symptom relief for a great number of patients, there is a risk of mesh complications following surgery, such as mesh exposure. In this situation, many patients require an additional surgery to revise their implant.

Mayo Clinic research, supported by the Center for Regenerative Medicine, is testing a regenerative approach to restoring form and function without additional corrective surgery in the setting of vaginal mesh exposure.

Vaginal prolapse is a medical term for a condition that leads to bulging of the pelvic organs, such as the bladder, uterus or rectum. It happens when ligaments and muscles on the pelvic floor stretch and weaken, no longer providing adequate support. Those internal organs slip down, bulging through the vagina wall, causing prolapse. Alternatively, women can also experience accidental leakage of urine with activity or cough, laugh and sneeze. This is termed stress urinary incontinence. Often linked to child birth, obesity or aging, incontinence and prolapse affect many women.  

Women with vaginal prolapse or urinary incontinence may choose to undergo placement of mesh if they have failed conservative therapies. Mesh is used in gynecology surgery to lift and support the pelvic organs, typically the bladder or uterus, relieving the pressure that caused the pelvic floor defect. However, like all surgery, there are potential risks. The mesh sometimes wears through the vaginal walls, causing vaginal discharge and possibly discomfort for women and their partners. Therein lies the dilemma: should there be another surgery to remove the mesh or would the patient prefer to live with the symptoms?

Mayo Clinic researchers are studying a new regenerative option, called purified exosome product (PEP) to treat a complication of the use of mesh in gynecologic surgery. Research, currently in animal models, is looking at whether PEP could promote regeneration of tissue that would grow over the mesh and restore the vaginal wall.

“While gynecological mesh is a viable option for many women, we wanted to create a non-surgical reparative option for our patients,” says John Occhino, M.D., clinician-scientist in gynecologic surgery with specialty training in urogynecology and pelvic reconstructive surgery. “We are studying the use of PEP to correct one of the most common side effects of mesh placement, the exposure of mesh through the vaginal wall after surgery.”

Exosomes are small membrane-bound vesicles secreted into the body’s cellular environment. Imagine bubbles carrying a signal that tell the body to regenerate and renew. For example, when the skin is scratched, exosomes are sent to repair the skin. By delivering a high dose of purified exomes, researchers can recruit numerous cells and pathways to help heal the tissue back to its original state.

“Our research injects an exosome gel into the vaginal tissues of a preclinical model of mesh exposure,” says Cassandra Kisby, M.D., female pelvic medicine and reconstructive surgery fellow. “Four weeks after treatment we saw the vaginal tissues had repaired and covered the prior mesh exposure.”

The regenerated tissues were physiologic, adds Dr. Kisby, meaning there were new blood vessels, the tissues had normal amounts of collagen, and there was minimal scaring.

Microscopic immunohistochemistry images showing areas of implanted mesh. The first image, treated with purified exosome product (PEP), has robust tissue regrowth (green) over the mesh and growth of the epithelium (red). The second did not receive PEP and has thin, broken tissue with little growth.

While this research is currently only being done in animal models, Drs. Occhino, Kisby and team are working to develop a phase 1 clinical trial to test the safety of PEP in humans within the next year.

“This technology opens the door for numerous applications in gynecology, including birth injury and repair, urinary incontinence, and fistulas.” says Dr. Kisby. “Our goal is to create a women’s health regenerative medicine program to help expedite the research and translation of this technology into clinical  practice.”


This story first appeared on the Center for Regenerative Medicine blog.

Editor’s Note: For more information about pelvic organ prolapse in women, specifically current knowledge regarding the incidence, appearance and management, read this recent article in UpToDate.

Mon, Jan 27 6:00am · Neuro regeneration for chemo brain: Mi-Hyeon Jang, Ph.D.

Cognitive dysfunction, sometimes called “chemo brain,” stemming from chemotherapy is a major adverse condition affecting approximately 14 million cancer patients and survivors in the United States. Although chemo brain has been widely reported by patients and clinicians, the cause of concentration and memory problems in cancer patients is not well understood. Mayo Clinic researchers are studying these effects in preclinical models in search of answers.

“Chemo brain is a frustrating side effect of cancer treatments,” says Mi-Hyeon Jang, Ph.D., associate professor of neurosurgery and assistant professor of biochemistry and molecular biology at Mayo Clinic. “Patients affected by chemo brain describe debilitating thinking and memory problems, including learning, memory and attention.”

Dr. Jang’s work to understand the cognitive deficits experienced by patients with cancer is funded by  Regenerative Medicine Minnesota. This understanding will provide insight into development of novel therapeutic interventions that prevent cognitive dysfunction, resulting in a better quality of life for cancer survivors.  To learn more, about Dr. Jang’s research in regenerative medicine, watch this video:

This story first appeared on the Center for Regenerative Medicine blog.


Mon, Jan 20 6:00am · Platelet rich plasma found to be effective in regrowing hair

Platelets spun from a person’s own blood may be a new option for treating baldness in women, according to research at Mayo Clinic’s Florida campus. A pilot study found platelet rich plasma (PRP), a regenerative therapy associated with natural growth factors and tissue healing, regrows hair as well as other treatments on the market. The findings could lead to new options for hair restoration beyond the pills or creams currently available.

Hair loss occurs when the cycle of hair growth and shedding is disrupted or when the hair follicle is damaged. There are several causes of hair loss, and not all treatments work for all hair loss.

Androgenetic alopecia is a type of hair loss known as male- or female-patterned hair loss. Researchers at Mayo Clinic’s Florida campus recently completed a clinical trial designed to validate platelet rich plasma to treat hair loss in women. The results, published in Journal of Dermatological Surgeryfound PRP to be effective in regrowing hair when injected into the skin of the scalp.  

Alison Bruce, M.D., Ch.B.

“Androgenetic alopecia is a challenging problem to treat, and many women are affected by this disorder,” says Alison Bruce, M.B., Ch.B., a Mayo Clinic dermatologist and principal investigator of the study. “It is typically very distressing to women, and there are limited treatment options currently available.”

Minoxidil, the current standard of care, is a topical treatment option. However, Dr. Bruce says the required daily application makes it difficult for patients to use. Alternatively, PRP uses the body’s own restorative capability to help restore and maintain hair growth. In this treatment, platelets are isolated from the patient’s own blood. The resulting concentrated platelets are then injected into the scalp.

The Research

In a randomized control trial, researchers followed 19 women with female pattern baldness.  The participants used topical minoxidil for 12 weeks followed by an 8-week washout between treatments and PRP scalp injections for 12 weeks. 

The Mayo Clinic study uses a high resolution camera and software to digitally count hairs, hair thickness, and hair density.

“Interestingly, both the PRP treatment and minoxidil worked to regrow hair,” says Shane Shapiro, M.D., medical director of the Regenerative Medicine Therapeutics Suites on Mayo Clinic’s Florida campus and co-principal investigator. “We now have scientific evidence that PRP works to temporarily regrow hair, offering patients more options for the treatment of hair loss due to androgenetic alopecia.”

Shane Shapiro, M.D.

The study found 21% of the volunteers had bruising or discomfort after PRP, but overall patient satisfaction was higher when treated with PRP than the minoxidil treatment. No adverse effects were reported during minoxidil treatment.

Mayo Clinic Center for Regenerative Medicine on all three Mayo Clinic campuses offers PRP cosmetically and medically for hair loss. 

“Many dermatology, cosmetic and regenerative medicine practices commonly promote PRP’s hair regenerating effect, but more study was needed to prove this,” says Dr. Shapiro. “Our research supports current literature confirming that PRP is effective in increasing overall hair count.”

Mayo Clinic Center for Regenerative Medicine seeks to translate regenerative therapies into the clinical practice. This is another example of how regenerative approaches may fill treatment gaps and provide patients additional choices for their health care. The study’s conclusions that both PRP and minoxidil can help regrow hair, may open new opportunities for Mayo Clinic physicians to combine these therapies for possible greater benefit than that of either treatment alone.


This story first appeared on the Center for Regenerative Medicine blog.

Nov 19, 2019 · Researching Stem Cells for Kidney Disease: LaTonya Hickson, M.D.

Regenerative Medicine Minnesota logo

Diabetic kidney disease (DKD) is a serious complication of diabetes. Up to 40 percent of people with diabetes eventually develop kidney disease. With no long-term treatment available, many patients will progress to end stage kidney disease requiring either dialysis or a kidney transplant. Research is underway to keep people from progressing to kidney failure, and the need for more invasive treatments such as dialysis or transplantation.

LaTonya Hickson, M.D., a Mayo Clinic nephrologist, is part of a research team looking at using stem cells to help regenerate failing kidneys.

“We take adipose tissue from a patient, harvest and expand mesenchymal stromal cells (MSCs), and later inject the cells into the patient’s injured kidney,” says Dr. Hickson. “Our hope is that these cells will then turn on the regenerative process to help delay the progression of kidney failure in individuals with diabetic kidney disease.”

Adipose-derived MSCs are stem cells that are taken from a patient’s abdominal fat and given back to the same patient. In this case, the cells are injected into the patient’s diseased kidney. Dr. Hickson’s latest research, a phase I clinical trial funded by a grant from Regenerative Medicine Minnesota, will assess the safety, side effects, dosing and timing of the delivery of these cells in patients with diabetic kidney disease.  

“This research could lay the foundation for the development of a therapy that may dramatically affect millions of patients across the country by altering the trajectory of diabetic kidney disease,” says Dr. Hickson.

While there’s a lot more research ahead, Dr. Hickson is excited about the possibilities. She discusses the research in the video below:

This story first appeared on the Center for Regenerative Medicine blog.


Nov 12, 2019 · Gerstner Regenerative Medicine Initiative: Tracking outcomes and supporting clinical trials

Image of an outcomes registry tablet used during consultations.
Outcomes registry tablet used during consults.

One of the challenges of integrating regenerative medicine into daily patient care is that it is so new, there is not a lot of available data to consider when determining best practices. A recent grant will help track information on how patient do after clinical trials.

The Gerstner Regenerative Medicine Initiative, funded through a grant from The Louis V. Gerstner Jr. Fund at Vanguard Charitable, is leading the design and implementation of a regenerative medicine outcomes registry and supporting ongoing osteoarthritis research and clinical trials at Mayo Clinic.

Regenerative Evidence-Based Outcomes Registry
The Regenerative Evidence-Based Outcomes Registry (REBO) is a digital platform used to track patient experience and patient outcomes for regenerative medicine procedures. It is one of three aims of the Gerstner Regenerative Medicine Initiative. In addition to a data collection repository, REBO is designed to be a digital learning platform that can show prospective patients outcome data in terms of effective treatments based on clinical conditions and other factors in order to help guide patient decision making and provide greater opportunities to make regenerative therapies available elsewhere in the Mayo Clinic practice.

“In order to contribute to high-quality real-world data and real-world evidence, we have created the REBO registry to track patients over time,” says Shane Shapiro, M.D., associate professor of orthopedic surgery and medical director of the Regenerative Medicine Therapeutic Suites in Florida who heads the Gerstner Regenerative Medicine Initiative. “Unlike traditional outcomes registries, we include additional elements that incorporate ethics and social information related to health outcomes of these innovative therapies.”

This means that researchers can apply real-world data in addition to rigorous clinical study data to expedite understanding of treatments and further the development of regenerative medicine products while also using this information to inform patients about regenerative options.

“Clinical research trials are tightly controlled and often start with small patient numbers which will exclude a larger representation of our patient population,” says Dr. Shapiro. “There are many additional sources of real world data including the electronic health record, insurance claims and even data that patients are willing to share with their providers from their phones and devices.”

Dr. Shapiro and his team intend to combine their real-world data with ongoing clinical studies to advance regenerative medicine therapeutics. The data can also be pooled with that of other practitioners and investigators in the field.

Jennifer Arthurs ARNP handing a outcomes registry tablet to a patient
Jennifer Arthurs, ARNP, handing an outcomes registry tablet to a patient.

The registry is built on a digital platform that can be customized to the needs of the practitioner as well as the health care field as a whole. This includes the ability to analyze the effect of medical comorbidities as well as behavioral concerns and mental health. The registry also weaves several medical and humanities specialties while educating and informing patients.

One of the first studies to use the REBO registry will track patient outcomes of shoulder and hip procedures.

“Almost all regenerative medicine clinical research is being conducted with knees,” says Dr. Shapiro. “By tracking patient outcomes for other joints, we can learn more about these procedures without even conducting additional trials.”

Regenerative Therapies for Knee Osteoarthritis
In addition to the REBO registry, Dr. Shapiro, through the Gerstner Regenerative Medicine Initiative, is spearheading a study to develop evidence-based best practices for dosing and frequency of regenerative therapies for knee osteoarthritis. The trial uses stromal vascular fraction (SVF) cells, or stem cells from a patient’s own fat, to treat pain from knee arthritis.

“There are many clinics out there irresponsibly marketing SVF cells directly to patients without approval from FDA,” says Dr. Shapiro. “This is an important trial because it is one of the first using SVF cells conducted in a legitimate scientific fashion to determine safety and efficacy, with all of the appropriate regulatory approvals.”

In all, the Gerstner Family Grant supports five initiatives across Mayo Clinic’s Arizona, Florida and Minnesota sites. Two of the five initiatives funded through the grant are designated to advance patient care through enterprise-wide regenerative medicine research and clinical trials at Mayo Clinic. Read more about the Gerstner family donation on the Mayo Clinic News Network.  

Watch an interview with Dr. Shapiro’s on how the Mayo Clinic Center for Regenerative Medicine is collecting real-world data to help inform patients, courtesy of The Evidence Base:

This story first appeared on the Center for Regenerative Medicine Blog.

Oct 25, 2019 · Regenerative strategies for osteoarthritis: Jonathan Finnoff, D.O.

Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage that cushions the ends of your bones wears down over time. While the significant pain, limited activity, and decreased quality of life that affect patients with osteoarthritis can usually be managed, the damage to joints can’t be reversed.

Finnoff, D.O.
, a physical medicine and rehabilitation specialist and medical
director of Mayo Clinic Sports
at Mayo Clinic Square in Minneapolis, is leading a study of regenerative
therapies as a treatment option when standard of care procedures do not work.
The study is funded through a Regenerative
Medicine Minnesota research grant

“One regenerative medicine option for those suffering from
osteoarthritis is the use of platelet rich plasma, or PRP,” says Dr. Finnoff. “While
there is mounting evidence that PRP injections may reduce pain and improve
function in people with osteoarthritis, we think we can make it better;
therefore, we’re looking to developing a safer, more effective alternative PRP treatment

PRP is made using a patient’s own blood. After the blood is
drawn, it is spun in a centrifuge which separates the cells and blood into
different layers. The concentrated layer of platelets, which is used for PRP, contains
proteins that are involved in the healing process and may also decrease
inflammation; however, PRP also contains some proteins that might trigger
inflammation of the breakdown of tissue.

“Our study involves trying to remove the inflammatory
proteins and those that might be involved in breaking down tissues from the PRP
so it has a stronger anti-inflammatory and healing affect,” says Dr. Finnoff.
“This is done by attaching proteins to tiny beads that bind to the proteins
that we want to remove from the PRP.”

Once a patient’s PRP product is developed, researchers will
then inject the new “purified PRP” back into the injured area to see if it is
effective to relieve osteoarthritis symptoms.

“Right now we treat osteoarthritis symptomatically with
weight loss, diet, exercise, braces, nutritional supplements, medications,
injections, and joint replacement surgery,” says Dr. Finnoff. “If we can
harness the healing potential of our body more effectively, we may be able to
slow the progression of arthritis or even reverse its course, revolutionizing
the treatment of osteoarthritis.”

Dr. Finnoff discusses his research in the video below:

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