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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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1 day ago · Regenerative Medicine Biotrust: advancing the practice through research

Regenerative medicine is a catalyst for innovation in health care, shifting the focus from treating symptoms of disease to unleashing the body’s ability to heal. Integral to the Mayo Clinic Center for Regenerative Medicine, the Center for Regenerative Medicine Biotrust is an important investment for Mayo Clinic. This unique resource enables physicians and scientists to develop regenerative technologies with the goal of bringing new cures to Mayo patients.  The Biotrust provides  resources, tools, technology and expertise to help Mayo Clinic scientists and physicians work collaboratively to advance regenerative sciences research from bench to bedside.

Dennis Wigle, M.D., Ph.D.

“It’s about supporting innovation and increasing therapeutic and diagnostic outputs,” says Dennis Wigle, M.D., Ph.D., chair of the Division of Thoracic Surgery and medical director of the Regenerative Medicine Biotrust. “The Biotrust offers a wealth of resources that would be hard for individual labs or investigators to develop on their own. It’s a pretty unique piece of infrastructure that few on the academic side have tackled.”

Mayo’s Center for Regenerative Medicine supports the Biotrust biorepository as one of its critical services to the clinical practice by facilitating the development of technologies that could lead to the manufacture of first-in-human therapeutics or development of novel diagnostic testing that will address the unmet needs of patients. 

What is the Biotrust?

The Biotrust offers clinical and laboratory-based services for researchers. It is like a scientific library that instead of books, collects and lends human biospecimens for the purpose of discovering new regenerative solutions. Patients donate tissue, mostly through skin biopsies, blood donations or adipose tissue collections. Stem cells are either derived directly from the tissues or generated using innovative technologies  to induce stemness. By providing access to living cells from  the Biotrust, Mayo Clinic researchers and their outside collaborators are able to speed the development of therapeutic and diagnostic technologies. Investigators may also use these stem cells to further investigational studies into the causes and progression of disease through disease in a dish modeling systems.  By doing so, this minimizes the impact on the patient by allowing investigators to detail the pathophysiology of disease and enable the testing of novel drugs prior to human trials. That could increase safety and avoid lengthy and costly human trials of non-efficacious drug candidates.

Zach Resch, Ph.D.

“The biggest value is expertise in obtaining samples from research subjects. For example, Mayo Clinic may have samples from a cohort of 20 patients with rare or orphan diseases. That gives us the ability to generate research materials at one institution rather than having investigators go to 20 different organizations,” says Zach Resch, Ph.D., operations manager of the Biotrust. “We have the capabilities to process and prepare samples under strict quality control that allows for storage and distribution across Mayo Clinic.”

Established in 2014 through a significant Mayo Clinic investment, the Regenerative Medicine Biotrust has grown its capabilities to include many new services, cell lines and disease applications. For example, the Biotrust has completed more than 1000 biopsies and dermal fibroblast isolations and derived mononuclear cells from 950 individual patients.

The Biotrust has the technology to reprogram adult stem cells harvested from skin for research and clinical application.  Reprogramming a patient’s cells is like bringing them a step back in time to when they were embryonic cells. At that time, cells were dividing and could become any type of cell or tissue in the body. Those reprogrammed cells are engineered to become induced pluripotent stem cells that can be redirected to become representative brain, heart, lung, bone kidney, pancreas and nerve cells. Reprogrammed cells can be grown and expanded within the Biotrust’s lab to meet research and clinical needs. The Biotrust offers over 400 unique induced pluripotent stem cell lines from healthy and diseased patients.

Additional services include:

  • Biomaterial validation
  • Project design
  • Regulated Distribution under institutional SCRO and IRB Biospecimens oversight 
  • Laboratory Training
  • Somatic and stem cell banking

Benefit to the patient

With induced pluripotent stem cells developed in collaboration with the Biotrust, Michael Ackerman, M.D., Ph.D., recently was able to use a disease in a dish model along with other genetic sleuthing techniques to describe two entirely new syndromes. One is triadin knockout syndrome, a heart arrhythmia that could lead to cardiac arrest in children during exercise. The second is an autosomal recessive genetic mechanism for calcium release channel deficiency syndrome, prevalent within Amish communities. That key discovery solved the mystery of why so many Amish children were dying suddenly during ordinary childhood play.

Additional examples of how the Biotrust is advancing research into disease include:

“I have patients who are interested in whether cell therapy might someday be a possibility for conditions like COPD. Contributing samples to the Biotrust may be one way they could help advance research that could someday help improve treatment for their disease,” says Dr. Wigle.

The Biotrust fosters continuous innovation in the emerging field of regenerative sciences. That may be particularly important to discovering and refining new regenerative cures for diseases that are prevalent in an increasingly aging population.

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This article orginally appeared on the Mayo Clinic Center for Regenerative Medicine blog.

6 days ago · Could regenerative medicine hold a key to understanding Alzheimer's disease?

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September is World Alzheimer’s Month, a time to raise awareness of research to unlock scientific mysteries around a disease that robs people of their memory, independence and ultimately their ability to think and reason. Focused on disease causes and cures, the Center for Regenerative Medicine is driving innovation as a collaborative partner in Mayo Clinic’s robust research to increase understanding and to slow or stop the progression of a neurological disorder for which there are no approved treatments to alter the course of disease.

Alzheimer’s disease affects 1 of every 10 people over the age of 65, or more than 5 million Americans, according to the Alzheimer’s Association. That number is expected to grow exponentially in coming years amid a rapidly increasing older adult population. Working collaboratively with Mayo Clinic’s Alzheimer ’s Disease Research Center, Center for Regenerative Medicine researchers are using the latest cellular technology along with regenerative approaches to better understand disease progression and possible regenerative treatments.

A regenerative approach to Alzheimer’s disease

Genetic, lifestyle and environmental factors are believed to play a role in Alzheimer’s disease. However, the biggest risk factor is advanced age. Neurological and memory decline — the hallmark of Alzheimer’s disease — is related mainly to two different types of proteins. The accumulation of amyloid-beta plaque interferes with neurons, resulting in a decline of brain cognition. Abnormal amounts of the protein tau causes tangles that become toxic and eventually kill the neurons in the brain. It’s a complex disease, however, and at the time of autopsy, many different abnormal proteins may be found in the brain.

Preclinical neuroscience research within the Center for Regenerative Medicine in Florida has focused on genetic risk factors linked to the apolipoprotein E (APOE) gene. The APOE gene has different versions called variants that impact the risk of Alzheimer’s disease. Laboratory studies that model the risk variant, APOE ε4, in mice discovered an increase degenerative effect on the brain, compared to the lower risk variant APOE ε3. 

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Guojun Bu, Ph.D.

“We found if we change this APOE genotype in the peripheral blood, it can affect brain cognition and amyloid-beta pathology. The ε4 genotype would impair brain cognition, but a switch to ε3 made the brain function better,” says Guojun Bu, Ph.D., chair of Neuroscience in Florida and associate director of Center for Regenerative Medicine in Florida. 

This discovery at Mayo Clinic in Florida has laid the foundation for phase I safety studies in humans. Researchers in Florida want to apply their genetic findings to the study of potential healing qualities of blood plasma. In particular, they want to answer the question of whether plasma from young donors without Alzheimer’s genetic risk factors would have regenerative effects on individuals with the APOE ε4 risk variant who are in the early stages of Alzheimer’s. Young donors would be people 30 years old or younger.

“We know from outside research that young plasma in general has a rejuvenating, regenerating ability  in age-related conditions and aging in general,” says Dr. Bu. “Testing whether an injection or even a complete exchange of young plasma might have therapeutic effects in early stage Alzheimer’s patients with the APOE ε4 gene variant is very intriguing.”

Currently, little is known about restorative healing in the aging brain. Traditionally, the brain has not shown to be prone to regeneration as it ages, according to Melissa Murray, Ph.D., a neurosciences researcher at Mayo Clinic in Florida.

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Melissa Murray, Ph.D.

“Our knowledge gained from neurodevelopmental studies suggests that specific signals are released when our brains are more plastic and capable of growth. Some focus has been paid to identifying if those signals could be turned on to facilitate regeneration,” says Dr. Murray. “There is still so much unknown, but neuronal regeneration should not be ruled out in this modern era of technological advances in stem cell therapy or with the potential for plasma donors.”

Creating mini brains to study Alzheimer’s disease

One of the hurdles to overcome in Alzheimer’s disease research is the absence of a model in which amyloid-beta plaques and tau tangles can be studied together. Animal models, which have been studied for years, don’t always reflect disease progression within the human brain.

“The mouse brain is quite different from the human brain anatomically and at the molecular level. Animal findings don’t always translate to humans,” says Dr. Bu.

The brain bank in Florida, which provides more than 5,000 post-mortem specimens, including 3,000 from Alzheimer’s patients, has been a key resource in advancing research into the cause and progression of neurodegeneration. The brain bank helps with defining how disease-associated pathologies correlate with gene expression, biomarkers and clinical information.

Now, researchers are taking their research a step further by growing human mini brains in a laboratory dish. Using induced pluripotent stem cells (iPSC) reprogrammed from skin fibroblasts or peripheral mononuclear cells, researchers are able to grow 3- to 4-millimeter living organoids resembling the structure of human brains including layers of neurons and ventricles. IPSCs are stem cells that are reprogrammed in labs but are similar to embryonic stem cells. They are now routinely generated in the Center for Regenerative Medicine infrastructural facilities such as Regenerative Medicine Biotrust and Neuroregeneration Lab. An embryonic cell can be redirected to become a brain cell for the purposes of creating a disease-in-a-dish for research.

“These living mini brains come from cells of individuals with Alzheimer’s disease,” says Dr. Bu. “With this model system, we can see more precisely what is happening within the Alzheimer’s brain and the effects of APOE ε4 gene variant. That helps us to study the cause and progression of the disease. We hope this brain-in-a-dish model will lead to an understanding of the Alzheimer’s pathology and how to target treatments that can slow or stop progression of the disease.”

When a therapy is someday identified, an individualized approach will be needed to successfully prevent or delay the onset of symptoms, Dr. Murray adds. 

“Treatment approaches are different for young onset Alzheimer’s disease, which develops in people under the age of 65, and late onset, which affects those over 65,” says Dr. Murray. “This is due to differences in where abnormal proteins accumulate and how often co-existing pathologies occur in the aging brain.”

Dr. Bu envisions future therapies that take a multi-pronged approach to treating amyloid-beta plaque, tau tangles and loss of neurons. Many phase I, II and III clinical trials are underway in the quest to move the latest laboratory discoveries into daily standard of care. Dr. Bu says realistically, it could take anywhere from five to 20 years for a drug to obtain Food and Drug Administration approval in the United States and bring new therapeutic options to Alzheimer’s patients.

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This article originally appeared on the Center for Regenerative Medicine blog.

Tue, Sep 15 6:00am · A regenerative alternative to hip replacement

Mikaili Robertson has a passion for playing college sports, so the second baseman was devastated when at age 18 he learned he needed a hip replacement. Worried his playing days might be over, he turned to Mayo Clinic and a surgery that — along with a cadaver tissue transplant — would tap the body’s power to assist healing. Mayo’s Center for Regenerative Medicine provided support for this procedure integral to its focus on bringing innovative regenerative treatments to patients.

Mikaili Robertson

“When people talked to me about hip replacement, I had visions of myself being like an old man with a walker, not able to do a whole lot. I started wondering what my quality of life would be like outside of baseball,” says Robertson. “My parents and I searched for alternatives to a hip replacement, and we found new options for hip surgery at Mayo Clinic.”

Robertson was a freshman playing baseball at Hood College in Maryland when his right hip started hurting after games. The diagnosis: sickle cell disease was choking off blood supply to the top of the hip joint known as the femoral head. Bone tissue began dying, causing a condition known as avascular necrosis, also called osteonecrosis of the hip.

Avascular necrosis also can be a rare side effect of heavy steroids used in some chemotherapies to treat cancer. It has been described as one of the unsolved mysteries of orthopedics. Once it starts, there is no known way of stopping the bone tissue from dying unless it is caught early. Without treatment 90% of patients with avascular necrosis will need a hip replacement.

Rafael J. Sierra M.D., and his colleague, Aaron Krych, M.D., are among a few orthopedic surgeons in the United States to perform a regenerative surgery called Fresh Osteochondral Allograft Transplantation Surgery (OATS) to the femoral head as an alternative for hip replacement in select patients with avascular necrosis. They are perfecting the surgery based in part on research in the Journal of Hip Preservation Surgery. Under a controlled dislocation of the hip, the dead bone can be removed and replaced with donor cartilage. Smaller lesions can be treated with transplants of the patient’s own cartilage. Larger areas of necrosis need cadaver cartilage-bone transplants. Bone marrow and stem cells spun from the patient’s own blood help the bone-cartilage transplant to fuse with the patient’s natural bone. Dr. Sierra describes it as a process similar to an organ or tissue transplant but without the need for immunosuppression to avoid rejection.

OATS is a regenerative option for patients like Robertson whose disease has progressed to an advanced stage in which the femoral head has collapsed, but still was located in a fairly circumscribed area and no permanent damage was present in the socket cartilage.

Rafael J. Sierra,
M.D.

“This regenerative procedure is saving some hips that in the past had deteriorated to the point that artificial replacement was the only possibility for restoring normal function,” says Dr. Sierra. “In the case of Mikaili Robertson, we removed approximately a quarter of the diseased femoral head in its weight bearing portion and completely carved out the necrotic area. We replaced that with allograft (donor bone-cartilage) that had been bathed in bone marrow concentrate and transplanted that into the top of the femur also known as the thigh bone. The normal bone that is left behind vascularizes the graft as if it were a native bone.”

As with any newly validated procedure, there are some risks with the OATS surgery.

“Because we have to expose the hip completely to dislocate it safely, there is a chance of more damage to the femoral head if one loses the blood supply, but I have not seen that in over 300 surgical hip dislocations. There’s a bone on the side of the hip (trochanter) that we have to cut and reattach with screws that may not heal, but that would be extremely rare. Overall, the risks are minimal, other than the possibility that this may not work, and the patient might need a hip replacement,” says Dr. Sierra.

For Robertson, it was a risk worth taking. He traveled to Mayo Clinic for the surgery in December 2018.

“It went as perfect as it could have gone.  It was a tremendous outcome of what was kind of uncertain for me,” says Robertson.

Robertson was off his feet during a three month recovery period, then he worked to regain his strength through physical therapy. He was cleared to return to baseball as a junior — until COVID 19 cut the season short. He has aspirations of helping his team win a championship in his upcoming senior year.

“That’s a big part of this success. I just got progressively back into running, lifting weights and working out, and I’m back on baseball team and playing. I’m back into full participation in sports and exercise and everything,” says Robertson, who is studying for a career in sports psychology.

Hip replacements are common standard of care procedures that meet the needs of many patients at Mayo Clinic.

“However, if we can avoid them, particularly for younger people, it is in the patient’s best interest over the long term,” says Dr. Sierra.

One previous study has shown that OATS procedures are still functioning successfully for 80% of patients 10 years after surgery. The results depend on the size of the lesion and the cause of the necrosis. That may be encouraging news for young patients like Mikaili Robertson, who have opted for this regenerative procedure as way of avoiding hip replacement, which could fail over time, resulting in a second replacement during the course of their lifetimes.

Mayo Clinic research continues to study, learn and improve regenerative procedures like OATS.

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

Tue, Sep 8 6:00am · Stem cell research to improve hemodialysis

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Stem cell therapy after angioplasty helps keep arteriovenous fistula blood vessels open, Mayo Clinic discovered in animal studies. An arteriovenous fistula is a passageway between an artery and a vein. This research, supported in part by the Mayo Clinic Center for Regenerative Medicine, provides a foundation on which someday patients with end stage renal disease, who require hemodialysis and whose vessels narrow and eventually fail over time, could be helped. The Center for Regenerative Medicine is committed to turning promising laboratory discoveries into proven treatments and making them available to patients.

Angioplasty — a procedure in which a thin tube attached to a balloon is threaded through vessels — is the first line of treatment to clear blockage for dialysis patients with stenotic arteriovenous fistulas, but may only be a temporary solution. Research by Sanjay Misra, M.D., published in the Journal of American Society of Nephrology, finds that mesenchymal stem cells derived from adipose (fat) tissue could prolong the therapeutic effects of angioplasty.

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Sanjay Misra, M.D.

“The best vascular access for hemodialysis patients is an arteriovenous fistula created by connecting the artery to the vein. Unfortunately, this type of fistula will eventually fail due to narrowing of the blood vessels that occurs over time,” says Dr. Misra. “Our peer-reviewed study shows that stem cells delivered to the outside of the vessel wall after angioplasty can help keep the vessel open longer.”

According to the National Kidney Foundation, approximately 2 million people worldwide with end stage renal disease undergo hemodialysis several times weekly to purify their blood. While there are a few different vascular options for dialysis to occur, arteriovenous fistula provides the best blood flow and also has less potential for life-threatening infections.

However, several studies have shown a recurrence of narrowing blood vessels in 40% of all hemodialysis patients one year after angioplasty.

“Currently there are more than 350,000 angioplasties per year are performed in the United States for hemodialysis arteriovenous fistulas” says Dr. Misra. “There are no durable therapies to prolong the opening of the vessels. Angioplasty plus stem cells may be a way to prevent stenosis, or narrowing of the vessels. In addition, this therapy could be used to address restenosis after arterial angioplasty.”

The research

Dr. Misra’s team compared two groups of mice with chronic kidney disease that had arteriovenous fistulas placed and had developed stenosis. Angioplasties performed on both groups expanded the narrowed vessels. Researchers injected some of the animals with adipose-derived stem cells and observed that group went a longer time without a recurrence of blockage than mice without stem cell therapy. Further, the team discovered that stem cells were still present as long as 28 days after injection, suggesting that the cells are providing benefit at this time point.

This study was funded in part by the National Institutes of Health. Prospective research in human clinical trials will be needed to verify the effectiveness and safety ofcombining adipose-derived mesenchymal stem cells with angioplasty to open blood vessels for dialysis patients with arteriovenous fistulas.

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

Tue, Sep 1 6:00am · Regenerating muscles after cancer surgery

Advancements in microsurgery are making it possible to harness the body’s healing power to regenerate muscle strength after some cancer surgeries, particularly surgery to remove soft tissue sarcomaMayo Clinic orthopedic oncologists are teaming with plastic surgeons in a procedure they’ve coined “oncoregeneration.” They are seeking to perfect this procedure in which large muscle is transferred to close a surgical wound and then coaxed to function like the muscle lost to cancer. This oncoregenarative surgery combines free muscle transfers with pain management and lymphatic reconstruction with a goal of restoring function, while preventing damaged nerves and lymph nodes that can cause pain and swelling.

Matthew Houdek, M.D.

“Quality of life after surgery is one of the biggest reason we started doing this surgery. Sarcoma patients were functional, but would get tired easily, mainly because they are relying on other muscle groups to restore the function that they once had. Sometimes being just OK after cancer surgery isn’t good enough,” says Matthew Houdek, M.D., an orthopedic oncologist at Mayo Clinic. “With this functional transfer, we are attempting to restore form and function of the muscle, so patients can get back to the lifestyles they once had.”

Every year there are more than 13,000 new cases of soft tissue sarcoma diagnosed in America, and 5,000 people will die from it, according to the American Cancer Society. Just a few decades ago, the only way to treat it was through limb amputation. In more recent years, cancer could be controlled by removing only the tumor, but patients often suffered severe limitations in mobility due to swelling, pain and loss of muscle. 

The procedure at Mayo Clinic is a free flap surgery done under a microscope with high precision tools smaller than the tip of a pen. These micro tools protect blood vessels, small nerves and small lymphatic vessels that can be less than 1 millimeter in diameter, so they can be transferred to the site of the tumor resection. Much like a plug placed in an electrical outlet, nerves and blood vessels from the healthy muscle are connected to the nerves and blood supply where the cancer was removed. That triggers a regeneration in which the transferred muscle may function like the one that had been removed.

Steven Moran, M.D.

“Advancements in microsurgical technique have made what we can repair and what we can restore much better.We now have the abilities to reconstruct and manage nerves in such a way that we minimize the chances of developing chronic phantom pain. We are also able to reconstruct the lymphatic channels to avoid painful fluid buildup and swelling that can limit mobility, also known as lymphedema. That’s a major improvement  for patients,” says Steven Moran, M.D., of the Mayo Clinic Division of Plastic and Reconstructive Surgery.

Regenerative Medicine Minnesota, a statewide bipartisan initiative to advance regenerative medicine research, education and practice, has awarded Dr. Moran and his team a grant to further examine the regenerative capacity of muscle. The research will explore opportunities for new regenerative therapeutics to restore muscle volume and muscle function after surgery or traumatic injury.

Like extra innings in a baseball game

For Mark Merila, oncoregenerative surgery was like the bonus of playing extra innings. The 48-year-old former professional baseball player and coach for the San Diego Padres defeated a rare brain tumor in the early 2000’s through chemotherapy and radiation. He transitioned to a job as a baseball scout for the Padres and despite having right side paralysis from the brain tumor, he enjoyed an active lifestyle. Then in 2018, a lump developed in his good leg that turned out to be an aggressive soft tissue sarcoma. Dr. Houdek had to remove two-thirds of Merila’s left quadriceps to get rid of all the cancer.

Facing the prognosis of life in a wheelchair or walking with a brace, Merila opted for the free flap surgery. Together Dr. Houdek and Dr. Moran transferred a portion of Merila’s latissimus dorsi (back and shoulder muscle) to Merila’s quadriceps, where it now functions like a normal thigh muscle.

Mark Merila

“You’ve heard the saying that a cat has nine lives. I feel like I’ve had nine-and-a-half lives. I’ve defeated cancer twice before the age of 50. I am very happy for the opportunity to have this surgery which has restored my ability to walk and, most importantly, to drive a car again,” says Merila. “This surgery has given me a new chance to go back to work and return to my normal activities, although at a slower pace.”

While transfers of smaller muscle groups in the upper body are more commonly performed, Mayo Clinic is one of the first to successfully perform functional free flap surgeries in larger muscles in the lower body.

“It takes expertise in lymphatic reconstruction, nerve reconstruction and muscle reconstruction. To find that in one medical institution is unique. The incredible teamwork at Mayo Clinic is what makes this possible,” says Dr. Moran.

“This is a huge step forward for our patients. We have some people who have gotten back to running, biking, jumping and nearly everything they want to do,” says Dr. Houdek.

The team at Mayo Clinic aspires to apply the oncoregenerative surgery to more types of large muscle transfers. As for Mark Merila, he hopes that with additional physical therapy, he will one day be able to get back to all his normal activities, including playing golf.

Mayo Clinic Center for Regenerative Medicine supports the work of physicians and scientist to advance the body’s ability to restore form and function toward a pre-disease state.

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

Tue, Aug 25 6:00am · Rock star baby hitting all milestones after fetal surgery

The first peek at her baby during the 20 week ultrasound turned from excitement to concern for Hetty Mollert.

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Tyler, Hetty and Madelyn Mollert
Summer 2019

“It was taking longer than I expected. I thought they were just being super in-depth about everything,” said Mollert, a first time mother-to-be from Madison, Wis. “Then we learned the devastating news. The ultrasound showed our baby had an opening in her spine. They believed she had spina bifida.”

The ultrasound revealed the baby had myelomeningocele, the most common and serious form of spina bifida. It’s a condition in which membranes and spinal nerves push through the opening in the spine, forming a sac and exposing tissues and nerves. This made Mollert’s baby prone to life-threatening infections and severe disabilities. The discovery launched Hetty and her husband, Tyler, on an emotional decision making roller coaster.

“I cried every night. Of all of the choices, termination of the pregnancy was not an option for us. That left us with two alternatives. We could have surgery while she was still in the womb to close the spine or we could do nothing and have surgery after she was born,” says Mollert.

The Mollert baby also had Chiari malformation, a neurological disorder related to spina bifida that pushes the brain down through the base of the skull. That condition may lead to a buildup of fluid on the brain known as hydrocephalus, which can damage the brain. Oftentimes, infants with hydrocephalus require a shunt after birth to drain the fluid.

The Mollerts did their research, and then weighed the risks and benefits. Fetal surgery would increase possibilities of preterm delivery, ruptured uterus, or death of the baby in rare cases. But, surgery after birth meant longer exposure of spinal cord nerves to amniotic fluid. That could cause more severe disabilities, including bowel and bladder disorders, mobility problems, paralysis and cognitive delays.
Approximately 1 in every 4,000 babies, or 1,645 infants every year, are born in the United States with myelomeningocele, according to the Centers for Disease Control and Prevention.

“At first we were not going to do the fetal surgery because of the risks,” says Hetty Mollert.  “However, I realized that all the things I listed as cons to fetal surgery were related to my own concerns and all the pros were in favor of the baby. We chose fetal surgery, because we believed it offered the best chance of reversing the brain malformation. We thought that might improve her chances of someday being able to walk.”

Rodrigo Ruano, M.D., Ph.D., fetal surgeon and chair of Mayo Clinic Division of Maternal Fetal Medicine and Edward Ahn, M.D., pediatric neurosurgeon, performed fetal surgery to close the spine at 25 weeks of gestation. Dr. Ruano theorized that closing the spine would decrease the fluid on the brain and that the body’s amazing ability to heal might take over and regenerate the developing brain. An MRI examination six weeks later while the baby was still in the womb found that Chiari malformation had been restored after fetal surgery. 

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Rodrigo Ruano, M.D., Ph.D.

“We discovered the main benefit of this procedure is not only to close the spine, but the most important thing is to improve the brain structure and the brain anatomy,” says Dr. Ruano. “Our study shows we can regenerate the brain structure so that it comes back to better development.”

She’s a rock star

Mollert was able to travel back to her hometown hospital and physician in Madison for her baby’s birth. Her daughter, Madelyn, was delivered via caesarian section at 37 weeks of gestation on January 11, 2019.

“From that point on, it was like a normal baby delivered in a normal pregnancy. The closure on her back looked fantastic. She did not need a shunt to release fluid from the brain. We went home after three days.  There was no stay in the neonatal intensive care unit,” says Mrs. Mollert. “Our physicians said Madelyn was a rock star.”

Madelyn has been hitting all developmental milestones.  At 13 months of age, she began standing on her own. Now, she is able to walk with assistance. That gives her parents confidence that she will one day be able to walk. But there are still some unknowns. Will she need leg braces to support her steps? Or, will she need a walker?  Also yet to be answered is whether fetal surgery improved chances of normal bladder and bowel function. That may not be known until she starts potty training. Indications so far are that her bladder health is on the right track.

“We just want to bask in the moment and enjoy how perfect she is now. We don’t want to worry about what might or might not happen years from now.”

Hetty Mollert believes her daughter is progressing better than if she’d had spine closure surgery after birth.  She’s healthy enough to go to daycare “and loves it,” says her mother, who works in human resources for a retail company. 

Madelyn Mollert is one of three consecutive spina bifida patients that Dr. Ruano studied to determine that surgery to close the spine before birth restored brain structure better than surgery after delivery. Dr. Ruano’s research is published in Mayo Clinic Proceedings.

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Read the news release.

This article was previously published on the Regenerative Medicine blog.

Tue, Aug 18 6:00am · Spotlighting 2020 graduates of Mayo Clinic College of Medicine and Science

Integrating new discoveries into patient care requires a workforce equipped to deliver the latest innovations. That’s why training the workforce of the future is a key objective of Mayo Clinic Education.

Every year, Mayo Clinic’s College of Medicine and Science advances new graduates to their next levels of research and/or medical practice to address the unmet needs of patients. From accelerating new ways to treat macular degeneration to discovering the latest immunotherapies that harness the body’s ability to heal, graduates of Mayo Clinic’s medical schools seek to apply the advanced diagnostics and novel therapeutics.

Sinibaldo Romero Arocha

Sinibaldo Romero Arocha

As a teenager in Venezuela, Sinibaldo Rafael Romero Arocha’s intrigue with American medical documentaries and television dramas inspired his career in biomedical research and regenerative medicine. His academic quests eventually led to the Regenerative Science Training Program (RSTP) in the Mayo Clinic Graduate School of Biomedical Sciences where he was one of the first graduates of the post-baccalaureate program.

“Many of the breakthrough discoveries I learned about in Venezuela happened at Mayo Clinic. I knew that if I wanted to be part of the next generation of scientists, this is where I should do my training,” says Romero Arocha. “Mayo Clinic was a fantastic training ground that helped prepare me for an M.D./Ph.D. program, which I will now be pursuing.”

While in RSTP, Romero Arocha trained in the cardiac regeneration research lab of mentors Andre Terzic, M.D., Ph.D., director of the Mayo Clinic Center for Regenerative Medicine, and Atta Behfar, M.D., Ph.D., deputy director for translation in the Center for Regenerative Medicine.

“We (trainees) were interested in trying to enhance therapies Dr. Behfar and Dr. Terzic had previously developed. My role was to help graduate students optimize the therapies to reduce cost of using the new technologies we were developing in the research lab,” says Romero Arocha.

During his time at Mayo Clinic, Romero Arocha had the opportunity to participate in the Regenerative Medicine and Surgery course, one of the first patient-focused regenerative sciences and surgery training programs in the country.  In addition, he was a leader in the Initiative for Maximizing Student Development program aimed at increasing the number of researchers from underrepresented socioeconomic backgrounds.

The mix of experiences he garnered through RSTP at Mayo proved to be a fertile training ground. He was accepted into the highly competitive, elite Oxford University-National Institutes of Health fellowship program which he will complete with the M.D./Ph.D. program at the University of Minnesota following his Mayo 2020 graduation from RSTP. He credits the rich training he received through RSTP with helping compete for and earn this prestigious fellowship. Romero Arocha will spend two years in medical school at the University of Minnesota, four years in the graduate fellowship program at the National Institutes of Health and two more years in medical school.

“RSTP exposed me to a lot of things that not every post baccalaureate has access to, such as a deep exposure to translational science and clinical trials. During my fellowship, I will be able to take my research training to the next level through exposure to groundbreaking research in many fields. It is such a huge honor,” he says.

Romero Arocha’s short term goal is to further research into ways stem cell therapy could improve treatment of macular degeneration. Still undecided about his long term clinical practice, he is interested in pursuing regenerative medicine and stem cell biology. Ultimately, he hopes to bring to his practice the vision of Mayo Clinic: the needs of the patient come first.

Rosalie Sterner, M.D., Ph.D.

While completing the Mayo Clinic Medical Sciences Training Program, Rosalie Sterner, M.D., Ph.D., played a critical role in developing education for fellow trainees in the nascent fields of immunotherapy and regenerative sciences. One of the challenges of training the next generation of physician-scientists is delivering new curriculum for subject matter that is dynamic and evolving. Dr. Sterner helped build coursework for the Regenerative T Cell Immunology in the Treatment of Cancer course, which offers graduate level credit through the Mayo Clinic Graduate School of Biomedical Sciences; selective credit through the Mayo Clinic Alix School of Medicine, and continuing medical education through a 2020 Updates in Chimeric Antigen Receptor (CAR)-T Cell Therapy course.

Rosalie Sterner, M.D., Ph.D.

“Immunology is readily applicable and highly important to understanding and potentially treating most disease. Gaining a better understanding of the immune system and gaining a better functional control of the immune system is critical in helping the body to better heal itself.” says Dr. Sterner.

As the student course director since 2017, Dr. Sterner worked for three years with faculty course director Saad Kenderian, M.B., Ch.B. and Karen Hedin, Ph.D., the-then Mayo Clinic Department of Immunology Graduate Program Director; Mayo Clinic Center for Regenerative Medicine Associate Director of Education and Sterner’s Ph.D. mentor through the Department of Immunology. Together, they refined the course every year. The continuing medical education (CME) course 2020 “Updates in CAR-T Cell Therapy” was one such avenue of growth. Dr. Sterner serves as a course director for this CME course along with hematology faculty Dr. Kenderian and Yi Lin, M.D., Ph.D.  Dr. Sterner was able to apply for and secure a Regenerative Medicine Minnesota multi-year grant to fund the course.

In 2020, she and the faculty had to quickly adapt to the social distancing guidelines of the COVID-19 pandemic and deliver the course online. Despite the last minute change, attendance among both physicians and students was strong. Dr. Sterner believes the team effort between the support staff, speakers, attendees, course directors, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic Department of Immunology, Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Regenerative Sciences Training Program, Mayo Clinic Alix School of Medicine, Mayo Clinic School of Continuous Professional Development speakers and Mayo Clinic Education Technology Center were critical to the course’s success.

Having graduated from the Mayo Clinic Medical Scientist Training Program in May of 2020, Dr. Sterner is now a resident in the highly competitive Mayo Clinic combined Joint General Surgery and Cardiothoracic Surgery Residency Program. Her goal is to become a cardiothoracic surgeon at an academic medical institution where she would have a research program of her own.

“From transplant to tumor immunology to many disease processes in between, immunology plays a critical role in cardiothoracic disease processes and potential development of treatments. These principles can potentially be applied to improving treatments of cardiothoracic diseases, and I plan to conduct research in these areas.”

The Iowa native looks forward to a career in medicine in which she can pursue her interests in research and education while helping people.

Somaira Nowsheen, M.D., Ph.D.

Growing up in Bangladesh as the daughter of two physicians, Somaira Nowsheen, M.D., Ph.D., knew she had a love for medical practice. However, she wanted to explore interests in research before committing to a career as a physician-scientist. After several years as a research technologist in various labs in the United States, Dr. Nowsheen enrolled in Mayo Clinic’s Medical Sciences Training Program in 2012.

Somaira Nowsheen, M.D., Ph.D.

“The unparalleled clinical training, the outstanding research opportunities and all in a collaborative supportive environment were some of the factors that attracted me to Mayo Clinic,” says Dr. Nowsheen.

Her background in research positioned her strongly to excel at Mayo Clinic, where she contributed to some 40 publications during the course of her M.D.-Ph.D. training program.  Among her many accomplishments, Nowsheen was named the recipient of the first Mayo Clinic M.D.-Ph.D. Program Director Achievement Award for outstanding research. The award is based on research achievements during the course of the Mayo Clinic Medical Scientist Training Program, which for Dr. Nowsheen included:

  • The Laura J. Siegel Breast Cancer Fellowship Award for “Regulation of BRCA1 and DNA double strand break repair”
  • The Vera Langan and Kieckhefer M.D.-Ph.D. Fellowships
  • The Agnes Hansen Award from the Xi Chapter of Graduate Women in Science 
  • Identification of the protein L3MBTL2 as a previously unrecognized component of the cell’s DNA damage response machinery, a result reported in a first-author paper in Nature Cell Biology
  • Three first-author papers describing the risk of cardiac toxicity after Herceptin treatment for breast cancer.

“I could not have asked for a better training program than the one I had at Mayo Clinic. I think the unique environment where medicine and research blends so seamlessly have helped make discoveries and innovation possible. For instance, for my Ph.D. thesis project, I collaborated with hematologists to access patient samples to validate my basic science research findings,” says Dr. Nowsheen.

A 2020 graduate of the Mayo program, Dr. Nowsheen will be doing her residency in dermatology at the University of California San Diego Medical Center after a transitional year at Gunderson Lutheran Medical Foundation.

“Dermatology is a field that encompasses medicine, infectious disease, immunology, and oncology. It offers a rich balance between clinical practice, translational research in cancer therapeutics, and teaching next-generation physicians,” she says.

Dr. Nowsheen looks forward to taking an individualized medicine approach to her research and practice to enhance therapeutic value of each patient’s treatments.

Besides Dr. Nowsheen, Dr. Sterner and Sinibaldo Rafael Romero Arocha, the other 2020 graduates across the five schools within the Mayo Clinic College of Medicine and Science undoubtedly have compelling stories of grit and achievement of their own to share. Mayo Clinic is committed to help propel their careers forward in order to cure, connect and transform medicine for generations to come.

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

Tue, Aug 11 6:03am · Expanding CAR T-cell therapy, welcoming Dr. Qin

The first time Hong Qin, M.D., Ph.D., saw images of how chimeric antigen receptor (CAR) T-cell therapy obliterated a tumor, he was captivated and inspired by this revolutionary treatment. As the new director of Regenerative Immunotherapies at Mayo Clinic in Florida, Dr. Qin and his team will play a pivotal role in accelerating the latest CAR T-cell and other regenerative immunotherapy discoveries from bench to bedside to address unmet patient needs.

Dr. Qin’s team will work with the Mayo Clinic Departments of Hematology and Medical Oncology, the Center for Regenerative Medicine and the Cancer Center in developing first-in-class CAR T-cell products, procedures and treatments. The goal is to position Mayo Clinic at the forefront of expanding regenerative immunotherapy options to more types of cancers and potentially neurological and autoimmune disorders.

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Hong Qin, M.D., Ph.D.

“When I was in medical school, I was taught that blood cancer was incurable. But with CAR T-cell therapy treatment, a significant number of patients with B-acute lymphoblastic leukemias can survive long term without the tumor coming back.  Such therapeutic benefits are unparalleled, and may go beyond traditional chemotherapy or radio therapy,” says Dr. Qin. “I believe that CAR T and regenerative immunotherapies in general will open a new era for Mayo Clinic to treat cancer patients.”

Immunotherapies unleash the body’s defense mechanisms to fight bacteria, viruses and diseases, including cancer. CAR T-cell therapy seeks to harness the power of the immune system by genetically modifying cells, equipping them to go on search and destroy missions to kill cancer. These engineered cells act like a living drug continually working within the body to cure disease.

The key hurdles to bringing CAR T-cell therapy to more patients are cost and access. It’s expensive and there are long waits for clinical trials.  Mayo Clinic is addressing those hurdles through the CAR T Translational Research Program that Dr. Qin leads.

New laboratory space will be made available in Florida for discovery science with the scope of attracting researchers with innovative ideas for developing new regenerative immunotherapy products unique to Mayo Clinic. For example, could scientists identify CAR T therapies with fewer side effects that are easier on patients? Could investigators discover ways to apply CAR T-cell therapy to solid tumors, providing new treatment options for many more types of cancer?

Mayo Clinic is one of only a few medical research centers that have made significant investments in facilities where clinical grade biotherapies can be manufactured on site. The new Discover & Innovation Building on the Florida campus will deploy current Good Manufacturing Practices (cGMP) facilities where new patient-ready immunotherapies can be manufactured under strict sterile quality control measures that meet Food and Drug Administration guidelines. That could eventually increase patient access to CAR T and other regenerative immunotherapies through clinical trials and lower the cost through in-house supply.

“With the cGMP facility we can help move new discoveries toward an initial clinical trial in order to perform critical first-in-man evaluation,” says Dr. Qin. “This platform is so important, because it empowers us to readily translate discoveries to the patient.”

The ultimate goal is to deliver the newly developed clinical grade immunotherapies to the medical practice to provide new hope and healing for patients.

Background in cancer research

Dr. Qin joined Mayo Clinic in June from City of Hope cancer research and treatment center in California, where he researched novel CAR T-therapies that are now in Phase I clinical trials.

Dr. Qin holds a medical degree from the Shanghai Second Medical University in China and a Ph.D. in Anatomy and Cell Biology from The University of Western Ontario in Canada. He has completed post-doctoral training and early career development as a junior faculty at the National Cancer Institute of the National Institutes of Health and the University of Texas M.D. Anderson Cancer Center. Dr. Qin holds seven patents related to antibodies and CAR-T therapies. 

“It is so important to translate emerging discoveries to the patient bedside, which can provide hope to cancer patients who have exhausted all other therapeutic options,” says Dr. Qin. “The team work at Mayo Clinic is so critical to having this mission accomplished.”

For Mayo Clinic, mission accomplished might mean robust research and development that delivers new cellular therapies providing new cures that so far have eluded patients.

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

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