Regenerative Medicine Minnesota (RMM) has awarded 13 grants totalling $4.3 million to support discovery, development, translation and commercialization of regenerative medicine-based innovations to improve human health in Minnesota and beyond.

The award-winning projects and awardees for 2024 are:

Clinical Trial Award:

Phase 1 Study of Intravenous Administration of Adeno-Associated Virus Gene Therapy for Individuals with Propionic Acidemia

Michael Barry, Ph.D., Mayo Clinic

Propionic acidemia (PA) is a severe metabolic disorder caused by mutations in the PCCA gene. Traditional treatments, including stringent life-long protein restrictions and liver transplants, have limited success and significant risks. This trial will evaluate the safety and preliminary efficacy of a groundbreaking gene therapy in young children, aiming to reduce metabolic crises, improve quality of life, and preserve cognitive function. The successful execution of this project will represent a significant advancement in the treatment of PA, offering hope to patients and their families.

Infrastructure Award:

Expanding Anatomic Infrastructure for Scaling Manufacturing Operations

Patrick Walsh, Anatomic Incorporated

Anatomic, a University of Minnesota start-up company based in Minnesota, develops neural tissues used in basic science and drug development. Its current flagship product, RealDRG, can be used to support development of novel non-opioid pain medications to address the ongoing, major unmet clinical need given the substantial life loss due to the opioid epidemic. This grant will support expansion of Anatomic's facilities to produce additional neural tissues that will enable researchers to understand central mechanisms of pain and amyotrophic lateral sclerosis (ALS) resulting in new therapies for these diseases.

Discovery Science Awards:

Reactivating Netrin1/DCC Signaling to Promote Optic Nerve Regeneration

Zhe Chen, Ph.D., University of Minnesota

Vision impairment that results from optic nerve damage, such as from glaucoma, poses a significant challenge to public health. To date, there are no effective therapeutics to block or reverse optic nerve degeneration, leading to irreversible vision impairment, including blindness. This project aims to identify molecular mechanisms that could be targeted therapeutically to promote regeneration of the optic nerve.

Human Microglia Model of Spinocerebellar Ataxia Type 1 (SCA1)

Marija Cvetanovic, Ph.D., University of Minnesota

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease with no disease modifying treatments or therapies available. Patients with SCA1 have relentlessly progressive movement and cognitive deficits and die prematurely 10 to 20 years from the disease onset. The goal of this project is to develop a human microglia (the immune cells of the brain) model of SCA1 to better understand the disease development and how mutations in the ATXN1 gene contributes to disease progression. Successful completion of this project will pave the way for future studies to develop therapies that will target and modulate microglia resulting in better treatments for patients with SCA1.

Illuminating Elusive Proteins Associated with Age-Related Macular Degeneration

John Hulleman, Ph.D., University of Minnesota

Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. Although variants in two genes—ARMS2/HTRA1—are the largest genetic contributor to AMD, their role in disease pathology has been challenging to study with existing methods. The goal of this project is to develop a new approach to gain insight into the pathobiology of ARMS2 and its relevance to AMD. Researchers will develop a series of stem cells that will eventually be used to identify new treatments that promote retinal health and prevent AMD-associated blindness.

A Novel Combined Allogeneic and Autologous Cell Therapy for Meniscus Tissue Repair

Daniel Saris, M.D., Ph.D., Mayo Clinic

Despite advanced surgical techniques, meniscus repair remains a significant clinical challenge due to high failure rates and chronic disability among young patients. This project aims to address this issue through a novel, one-stage cell therapy combining allogeneic adipose-derived mesenchymal stem cells and autologous meniscus cells to promote regeneration. This therapy builds on the researchers' pioneering work with a similar approach for cartilage injuries, which showed promising results in clinical trials. The anticipated outcome is a paradigm shift in meniscus injury management, significantly reducing long-term disability and improving quality of life for young patients.

Translational Research Awards:

Feasibility of Reducing Inflammation and Lung Injury to Regenerate Lung Tissue Using an Extracellular Biotherapeutic Aerosol in a Model of Acute Respiratory Distress Syndrome (ARDS)

Bryce Beverlin II, Ph.D., Quench Medical

Acute respiratory distress syndrome (ARDS) is a severe form of lung injury and a common cause of respiratory failure. Effective drug therapies that address underlying mechanisms have not been realized and ARDS remains a leading cause of death in critically ill patients. Biologic therapeutics derived from mesenchymal stem cells and exosomes are currently being evaluated as a therapeutic strategy. However, their effectiveness is limited by the ability to reach the lungs. To overcome this limitation, Quench Medical is developing a minimally invasive inhaled biologic aerosol that delivers exosome-based therapeutics directly to lung tissues. This project aims to demonstrate the efficacy of this approach in reducing inflammation from ARDS and regenerating damaged lung tissue.

Cryopreservation of Pancreatic Islets to Achieve Diabetes Cure through Transplantation

Erik Finger, M.D., Ph.D., University of Minnesota

Diabetes is a debilitating disease that has a tremendous impact on a person's health and wellbeing. Pancreatic islet transplantation offers a potential cure, yet an insufficient quantity of high-quality islets currently limits the success of this treatment. A method for cryopreserving or “banking” of islets prior to transplant can achieve the high viability, function, and clinical scalability required for human transplantation. This study will validate the function of cryopreserved islets using the novel technology cryomesh vitrification-rewarming with the goal to launch a clinical trial of vitrified islet transplants to increase accessibility of pancreatic islet transplants to cure diabetes.

Rotator Cuff Regeneration Using BMP5

Scott Riester, M.D., Ph.D., Mayo Clinic

Rotator cuff disease causes severe shoulder pain and limited arm movement. Current treatments offer temporary relief but do not regenerate damaged tendons. Preliminary studies show that injections of the biologic agent BMP5 can improve tendon strength by 30 percent. This project aims to complete pre-clinical studies to evaluate BMP5’s safety for rotator cuff treatment and has the potential to provide a new regenerative treatment option and reduce the need for surgery.

Optimized Chimeric Antigen Receptor T Cell Therapy for Colorectal Cancer

Omar Gutierrez Ruiz, Ph.D., Mayo Clinic

Colorectal cancer (CRC) is the third most common cancer in Minnesota, yet current treatments for advanced CRC have low survival rates. This project aims to develop a targeted cell therapy that enhances the killing of cancer cells and disrupts the tumor microenvironment. The researchers will further optimize this therapy in preclinical models, paving the way for a Phase I clinical trial to improve outcomes for CRC patients.

Use of Human Lung Exosomes to Prevent Ischemia/Reperfusion Injury in Lung Transplantation

Sahar Saddoughi, M.D., Ph.D., Mayo Clinic

This study aims to mitigate ischemia reperfusion injury (IRI), a major cause of primary graft dysfunction in lung transplants, by using an FDA-approved lung spheroid cell exosome (LSC-Exo) therapy. Preliminary studies show that LSC-Exo improves lung function and reduces IRI. Researchers will test LSC-Exo in a lung transplant model and in human donor lungs rejected for transplant. Their goal is to enhance lung transplant outcomes, increase the number of usable donor lungs, and improve patient survival and quality of life. Successful completion of this study will pave the way for clinical trials.

Functional Correction of Mucopolysaccharidosis Type I (Hurler Syndrome) Using Genetically Modified Autologous Memory T Cells

Nicole Shirkey-Son, Ph.D., Kommodo Therapeutics

This study aims to develop safer and more effective therapies for patients with a class of genetic diseases, called enzymopathies resulting from missing or defective enzymes. Current therapeutic approaches fail to stop disease progression and adequately replace deficient enzymes. Researchers are developing a novel cell-based therapeutic approach using genetically modified autologous memory T cells that is capable of delivering sustained enzyme replacement. In this project researchers will complete studies on efficacy, safety, dosing, and manufacturing that are critical for translating their novel cell-based therapy for MPS I. Successful completion of this project will advance this therapeutic approach into a clinical trial to improve outcomes for patients with MPS I.

Androgen Receptor Blockade to Augment Liver Regeneration

Rory Smoot, M.D., Mayo Clinic

A liver resection, or hepatectomy, is a surgical procedure to remove part of the liver. Post-hepatectomy liver failure is a major complication, with no approved treatments currently available. This project focuses on repurposing an FDA-approved drug to enhance liver regeneration, addressing a significant unmet need for patients undergoing liver resection. Researchers will assess the efficacy and safety of this approach, ensuring it does not promote tumor growth. Successful completion of these studies will pave the way for clinical trials, potentially offering a new therapeutic option to prevent or treat post-hepatectomy liver failure and significantly improve patient outcomes.

2025 Request for Proposals

For 2025 awards, RMM is calling for transformative proposals aimed at overcoming barriers that currently prevent or hinder regenerative medicine therapies from getting into patients. Key barriers to translation in regenerative medicine include availability of preclinical models and human microphysiological systems, lengthy and expensive development timelines, scalability of manufacturing processes and product consistency. RMM aims to support projects that leverage strengths in Minnesota to overcome these barriers and position the state at the forefront of regenerative medicine. Letters of Intent are due Nov. 8. Learn more at www.regenmedmn.org/apply-grant

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About Regenerative Medicine Minnesota

Regenerative Medicine Minnesota was established in 2014 by the Minnesota State Legislature to improve the health of Minnesotans by advancing regenerative medicine. This state-wide initiative opens new economic opportunities through commercialization of technologies and leverages the strengths of Minnesota institutions to position the state at the forefront of regenerative medicine. The initiative distributes approximately $4 million in funding statewide every year for research, commercialization, and clinical translation initiatives that improve or increase access to scientifically proven regenerative medicine throughout the state. Learn more at www.regenmedmn.org.

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Related stories:

Regenerative Medicine Minnesota awards three grants to Mayo Clinic researchers

Regenerative Medicine Minnesota awards five research grants to Mayo Clinic

The post Regenerative Medicine Minnesota awards 13 research grants for 2024 appeared first on Mayo Clinic News Network.

Katy Lydon was in fifth grade when she became enthralled with engineering. A team of engineers visited her classroom and led an exercise in designing, building and testing miniature towers made out of cardboard. But she didn’t associate engineering with medicine until the end of high school. "I didn't truly learn about biomedical engineering until my senior year," she says of the field that became her passion, "and I wished I'd been introduced to it earlier."

Now a third-year Ph.D. candidate at Mayo Clinic Graduate School for Biomedical Sciences, Lydon conducts research under the mentorship of orthopedic surgeon Daniel Saris, M.D., Ph.D., whose basic science lab specializes in restoring function to injured joints through cell and tissue repair,  especially for knee injuries. Even as Lydon conducts experiments, she remains interested in educating others about what biomedical engineers do. So, when the National Institutes of Health announced its annual contest to introduce biomedical engineering concepts to middle schoolers, Lydon was all-in. She set out to draft a classroom plan.

"I knew it would be out of my comfort zone," she says, "but I loved that the NIH is aiming to introduce kids early to engineering — and to biomedical engineering, specifically." This month she learned the lesson plans she developed were among five national winners of the National Institute of Biomedical Imaging and Bioengineering contest — known as the Biomedical Engineering Adapted for Middle Schoolers (BEAMS) Challenge — with a $5,000 prize. Through the National Institute of Biomedical Imaging and Bioengineering, the winning lesson plans will be provided free for teachers around the country to use in their classrooms.

Connecting with kids (and keeping their attention)

As a graduate student, Lydon's research focuses on restoring a torn meniscus, a knee injury that's notoriously challenging to treat. The team in Dr. Saris' lab studies various approaches to generate new tissue for the knee and also conducts biomechanical tests to understand the durability of the engineered product. When Lydon decided to develop lesson plans for middle schoolers, she chose the topic of "biomaterials" — natural or synthesized substances that can be used to solve medical issues. Biomaterials can include the metals or ceramics used in a hip replacement or even the polymer scaffold used as a base to grow engineered tissue.

The first challenge she faced, however, was finding an approach that would make sense to young students. "The way we think as researchers is very different from the way you have to address a middle school classroom," she acknowledges. "There's so much information that goes into knowing what a biomaterial is, how it's used, what its properties are, but in this case, you need to use vocabulary middle schoolers use. And you have to keep them focused."

After packing a PowerPoint with information, Lydon realized quickly she had to pare back and share details students could engage with and retain. She worked closely with Christopher Pierret, Ph.D., assistant dean of academic affairs, who also leads the Mayo-initiated science-training program InSciEd Out that takes place in schools. Dr. Pierret encouraged Lydon to include hands-on activities for the students.

"What's exciting about the BEAMS initiative is the intent to connect classroom education to the cutting-edge of science related to biomedical engineering, but it's an initiative that's great for the entrants, too," Dr. Pierret says. "It's a fantastic opportunity for new scientists to experience curriculum-writing. Our graduate school encourages students to broaden their competencies for paths after graduation. In a short period of time, Katy learned about education practice, theory and strategy."

Lydon also met individually with two teachers from Rochester-area schools and shared her draft lesson plans. "They were honest and gave open feedback," Lydon says. "They were able to say, 'No the students won't sit for this' or 'the small groups need to be smaller.' I knew going into the meetings with them that a lot of what I'd developed was going to have to change before I had a final product. Their input was incredibly valuable."

The materials doctors use to help patients

In the first of four 45-minute lessons, Lydon's classroom plan invites students to sort different biomaterials they find in a box, identifying what the objects are made of and describing their properties. As they learn specific types of biomaterials, such as metal, ceramic or polymer, they learn how the materials are used by doctors to help patients. (Some materials make good stents, as Lydon explains, while others make good prosthetic joints.)

All along, students are prompted to think about questions such as the advantages and disadvantages of certain materials, how their properties help with their intended function and even the environmental impact of each substance. After doing short readings, sharing information in small groups and even playing a Jeopardy-style game about biomaterials, the students' learning culminates in designing a mock device out of pipe cleaners and other easily accessible items that could address a medical problem.

The two middle school teachers Lydon consulted with expressed interest in using the lesson plans. "They were very enthusiastic about trying this out," she says.

Ultimately, her participation in the contest is important for the field, and for Mayo, too, says Leigh Griffiths, MRCVS, Ph.D., dean of the graduate school. "We all play a role in sharing the importance of science, even with the youngest learners, and training the workforce of the future," he says.

For Lydon, the joy was in creating a middle school experience she wished she'd had as a kid. "It was great to think about relaying these complex topics in a way that middle schoolers can understand, whether it's dealing with a broken bone or healing a knee, and sharing how biomedical engineering can be used to solve problems that matter to all of us," she says.

—Kate Ledger

The post Sharing a passion for biomedical engineering with young students appeared first on Mayo Clinic News Network.

"I've always been intrigued with understanding how science and biology work and how we can use it to our benefit," says Dr. Saris. "I was drawn to orthopedics, because it is a surgical expertise that focuses on quality of life and the tangible improvements it can make in the lives of patients."

Dr. Saris works on joint preservation at Mayo Clinic. His research investigates cellular therapies that repair cartilage defects. Dr. Saris compares it to filling potholes to fix a road rather than replacing the entire street.

"If we can treat the 20- to 50-something-year-olds with a new biotherapeutic that repairs cartilage and enables them to use their own joints for years to come, that's a significant benefit to them," says Dr. Saris. "By enabling their active lifestyle and delaying their first joint replacement until they are older and a little bit less active, they are likely to have a better outcome."

Mayo Clinic's Center for Regenerative Biotherapeutics is leading biomanufacturing strategy to accelerate new cellular therapies to early-stage clinical trials and, eventually, to clinical care. The center supports Dr. Saris' research as part of its objective of delivering new cures to the practice, particularly for rare and complex conditions.

Seeking cellular solutions

Dr. Saris is the principal investigator of a clinical trial that is testing use of a regenerative cell therapy to repair damaged cartilage with just one surgery. In this research, healthy cartilage from a patient is recycled and mixed with donated mesenchymal stem cells from Mayo Clinic's stem cell bank. Mesenchymal stem cells are adult stem cells that have been well studied and have shown healing potential. Dr. Saris' team uses the cell mixture to plug holes in the cartilage and then documents the results.

"In our research, we are mixing the patient's cartilage cells with donor stem cells, a one-step procedure to study how that facilitates cartilage growth in the knee," says Dr. Saris. "Our research enables us to understand how cartilage cells talk to mesenchymal stem cells and the role that plays in repairing tissue."

Dr. Saris' team has studied this procedure in a phase one safety study of knee cartilage damage and now a phase one study of hip cartilage damage.

Tears in cartilage — the connective tissue that lines the joints — are a common problem from sports injuries, falls or daily wear and tear. A tear often affects the knee, but can happen in the hip, ankle, elbow or shoulder. Left untreated, cartilage damage typically gets worse and can lead to osteoarthritis and joint replacement.

"Cartilage does not have a blood supply or nerves. That means when it is damaged, it does not heal by itself," says Dr. Saris.

Cartilage injury can happen at any age but is particularly troublesome for active adults under the age of 55 who are not ready for joint replacements. Options for preserving joints among this age group have traditionally been limited.

Tears in cartilage — the connective tissue that lines the joints — are a common problem from sports injuries, falls or daily wear and tear. Left untreated, cartilage damage typically gets worse and can lead to osteoarthritis and joint replacement.

Dr. Saris believes that regenerative medicine holds the key to delivering new biotherapeutics for cartilage repair and many other unmet patient needs.

"As people live longer across the world, we will be confronted with more diseases," says Dr. Saris. "We have to come up with smarter solutions to make sure that we have a good quality of life as we grow older. One solution is regenerative medicine and using the body's own capacity to heal and correct disease."

About Dr. Saris

Dr. Saris graduated from the University of Amsterdam Medical School. Following that, he came to Mayo Clinic for a research fellowship in orthopedics, cartilage and biomechanics. Dr. Saris then completed his Ph.D. and a residency in orthopedics at the University of Utrecht in the Netherlands.

He came back to join the physician staff at Mayo Clinic in 2018, where he applies his love of science to continual improvements in the techniques of joint preservation.

"I wouldn't be satisfied doing the same thing for 30 years and not finding a way to improve it for the benefit of patients," says Dr. Saris.

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Research by Dr. Saris:

Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial

The post Science Saturday: Like filling a pothole — cell therapy for cartilage repair appeared first on Mayo Clinic News Network.

Knee pain is a common problem that can have many causes, but one common reason is damage to the cartilage. Because cartilage doesn't have its own blood supply, it can't heal itself. When knee cartilage is damaged, treatment options are available, including a new method using a patient’s own cells to grow new cartilage. The new technique is called matrix-associated autologous chondrocyte implantation, or MACI.

On the Mayo Clinic Q&A podcast, Dr. Daniel Saris, an orthopedic surgeon at Mayo Clinic, discusses MACI, the regenerative medicine approach to treating knee cartilage damage.

Watch: Dr. Saris discusses treatment for knee cartilage damage

For the safety of its patients, staff and visitors, Mayo Clinic has strict masking policies in place. Anyone shown without a mask was recorded prior to COVID-19 or in an area not designated for patient care, where social distancing and other safety protocols were followed.

The post Mayo Clinic Q&A podcast: Using regenerative medicine to treat knee pain appeared first on Mayo Clinic News Network.

On the Mayo Clinic Radio podcast, Dr. Sophie Bakri, an ophthalmologist at Mayo Clinic, explains macular degeneration and shares her new research on treatments for macular disease. Also on the podcast, Dr. Christopher Camp, an orthopedic surgeon at Mayo Clinic, discusses treatment options for frozen shoulder. And Dr. Daniel Saris, an orthopedic surgeon at Mayo Clinic, and Dr. Aaron Krych, an orthopedic and sports medicine specialist at Mayo Clinic, explain recycled cartilage auto/allo implantation, or RECLAIM — a novel stem cell therapy using regenerative medicine for knee cartilage repair.

The post #MayoClinicRadio podcast: 1/19/19 appeared first on Mayo Clinic News Network.

On this week's Mayo Clinic Radio program, Dr. Sophie Bakri, an ophthalmologist at Mayo Clinic, will explain macular degeneration and share her new research on treatments for macular disease. Also on the program, Dr. Christopher Camp, an orthopedic surgeon at Mayo Clinic, will discuss  treatment options for frozen shoulder. And Dr. Daniel Saris, an orthopedic surgeon at Mayo Clinic, and Dr. Aaron Krych, an orthopedic and sport medicine specialist at Mayo Clinic, will explain recycled cartilage auto/allo implantation, or RECLAIM — a novel stem cell therapy using regenerative medicine for knee cartilage repair.

Here's your Mayo Clinic Radio podcast.

The post Macular degeneration / frozen shoulder / regenerative cartilage repair: Mayo Clinic Radio appeared first on Mayo Clinic News Network.

Macular degeneration is a common eye disease and a leading cause of vision loss among people 50 and older. With macular degeneration, the center of your retina begins to deteriorate. This causes symptoms, such as blurred central vision or a blind spot in the center of the visual field. There are two types: wet macular degeneration and dry macular degeneration. Many people will first have the dry form, which can progress to the wet form in one or both eyes. In some people, age-related macular degeneration advances so slowly that vision loss does not occur for a long time. In others, the disease progresses faster and may lead to a loss of vision in one or both eyes. Early diagnosis and treatment can help patients maintain their vision.

On this week's Mayo Clinic Radio program, Dr. Sophie Bakri, an ophthalmologist at Mayo Clinic, will explain macular degeneration and share her new research on treatments for macular disease. Also on the program, Dr. Christopher Camp, an orthopedic surgeon at Mayo Clinic, will discuss  treatment options for frozen shoulder. And Dr. Daniel Saris, an orthopedic surgeon at Mayo Clinic, and Dr. Aaron Krych, an orthopedic and sports medicine specialist at Mayo Clinic, will explain recycled cartilage auto/allo implantation, or RECLAIM — a novel stem cell therapy using regenerative medicine for knee cartilage repair.

To hear the program, find an affiliate in your area.

Use the hashtag #MayoClinicRadio, and tweet your questions.

Mayo Clinic Radio is on iHeartRadio.

Access archived shows or subscribe to the podcast.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Mayo Clinic Radio: Macular degeneration appeared first on Mayo Clinic News Network.

On this week's Mayo Clinic Radio program, Dr. Sophie Bakri, an ophthalmologist at Mayo Clinic, will explain macular degeneration and share her new research on treatments for macular disease. Also on the program, Dr. Christopher Camp, an orthopedic surgeon at Mayo Clinic, will discuss  treatment options for frozen shoulder. And Dr. Daniel Saris, an orthopedic surgeon at Mayo Clinic, and Dr. Aaron Krych, an orthopedic and sports medicine specialist at Mayo Clinic, will explain recycled cartilage auto/allo implantation, or RECLAIM — a novel stem cell therapy using regenerative medicine for knee cartilage repair.

To hear the program, find an affiliate in your area.

Miss the show?  Here's your Mayo Clinic Radio podcast.

Use the hashtag #MayoClinicRadio, and tweet your questions.

Mayo Clinic Radio is on iHeartRadio.

Access archived shows or subscribe to the podcast.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Mayo Clinic Radio: Macular degeneration / frozen shoulder / regenerative cartilage repair appeared first on Mayo Clinic News Network.