Orthopaedics Department’s Regenerative Research Highlighted at ORS Annual Meeting

Miller School faculty and students discuss developing personalized therapies to slow and reverse osteoarthritis progression.

University of Miami Miller School of Medicine orthopaedic research on regenerative medicine for osteoarthritis dotted the presentation agenda at the Orthopaedic Research Society’s (ORS) Annual Meeting.

ORS uses the meeting as an opportunity to highlight interdisciplinary research, an area of emphasis for the Miller School’s Department of Orthopaedics.

“Miller School faculty and students had multiple poster presentations featuring our department’s university-wide collaborations, including colleagues from engineering, as well as the Hussman Institute,” said Thomas Best, M.D., Ph.D., professor of orthopaedics and vice chair of research at the Miller School.

Members of the Miller School's Orthopaedics Department at the 70th Orthopedics Research Society (ORS) annual meeting
Members of the Miller School’s Department of Orthopaedics, including Dimitrios Kouroupis, Ph.D. (second from left) and Thomas Best, M.D.. Ph.D. (far right), at the Orthopedics Research Society Annual Meeting.

The department is aggressively pursuing regenerative treatments for osteoarthritis, a growing concern in an aging population for a problem that lacks disease-modifying agents, according to Francis Hornicek, Jr., M.D., Ph.D., professor and chair in the Department of Orthopaedics at the Miller School.  

“The research we’re doing is so important, as it is generating findings that could lead to therapies to treat the underlying disease and not just the symptoms,” Dr. Hornicek said.

Osteoarthritis Not a Single Disease

Eight studies by Miller School researchers were selected for this year’s ORS meeting, according to Dimitrios Kouroupis, Ph.D., assistant research professor of orthopaedics at the Miller School.

“Many academic groups around the world, including ours, strongly believe and are showing in studies that osteoarthritis, or OA, is not a single disease,” said Dr. Kouroupis, who co-authored most of the Miller School studies presented at the meeting and mentored the students who attended and presented. “In fact, it probably has multiple phenotypes.”

Dimitrios Kouroupis, Ph.D. left) and Thomas Best, M.D.. Ph.D., stand in front of a poster at the OST annual meeting.
Dr. Kouroupis (left) and Dr. Best at the ORS Annual Meeting.

That suggests physicians need to understand the phenotype before prescribing OA treatment. In the future, a doctor might be able to use a patient’s OA phenotype to prescribe a more specific, effective treatment.

“That’s the essence of precision or personalized medicine, an area in which we are making headway at the Miller School by exploring potential molecular phenotypes,” Dr. Best said. “We also are one of the most experienced orthopaedic research teams in small, extracellular vesicles or exosomes studies. We are collaborating on some of that research with one of the country’s leading sports medicine programs, the Steadman Philippon Research Institute.”

ORS Annual Meeting Highlights

Miller School researchers worked with the Steadman Philippon Research Institute on one study presented at the meeting, “CD10-Bound Human Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles Possess Immunomodulatory Cargo and Maintain Cartilage Homeostasis under Inflammatory Conditions.”

Another study Miller School researchers presented, “Infrapatellar Fat Pad Mesenchymal Stem/Stromal Cell Derived Exosomes for Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) Inhibition: Potential Implications for Inflammation/Pain Reversal,” was a multi-department look at taking small extracellular vesicles from the fat pads in the knee.

“It turns out fat pads have a lot of mesenchymal stem cells that secrete anti-inflammatory, analgesic and reparative small extracellular vesicles,” Dr. Kouroupis said. “We looked at the ability of these vesicles to target molecules, which we’ve identified and know have a lot to do with pain, to see if we can modulate pain and inflammation.”

The work could serve as a foundation for therapeutics that resolve detrimental aspects of immune-mediated inflammatory joint changes associated with conditions like osteoarthritis.

In the poster presentation, “Hippo Signaling Modulates the Mechanoresponses of NFκB in Chondrocytes via PKC,” Miller School researchers suggest a specific molecular pathway as a potential phenotype for treatment of post-traumatic osteoarthritis.

In another paper featured at ORS, “Human Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles Diffusivity in Meniscus Tissues,” Miller School orthopaedics researchers collaborated with engineering colleagues, a testament to the power of university-wide collaborations, according to Dr. Best.

“In this paper, we look at whether small, extracellular vesicles are able to diffuse into meniscus tissue. Meniscus tears are common, not often repairable and, if the meniscal tear is surgically removed, it increases patients’ risk for osteoarthritis,” Dr. Best said. “This work could result in ways to improve meniscal tissue function. We found these vesicles do have the ability to diffuse into meniscus tissue, so the next step is studying these vesicles in a preclinical model of degenerative meniscal tears to determine if we can improve healing capacity.”

The study on which the paper is based, “An Inverse Finite Element Analysis Approach to Model Meniscus Tensile Behavior,” uses a computational model to examine how the changing properties of the meniscus affect meniscal mechanics.

Still other Miller School-led research at ORS, including “Ultrasonic Assisted Coating of Fused Deposition Modeling Based Poly Lactic Acid Scaffolds for Improved Load Bearing Strength,” “Biomechanical Analysis of Atlantoaxial Fixation Techniques in an Osteoporotic Cadaver Model” and “The Role of Oxytocin-primed Human Mesenchymal Stem/Stromal Cells in Reversing Macrophage Pro-inflammatory Phenotype,” represent multidisciplinary collaborations aimed at improving care of orthopaedic patients.

“We are proud of our students for contributing to these novel studies and attending a prestigious meeting, like ORS,” Dr. Kouroupis said. “One of the many strengths of the Department of Orthopaedics is the exposure we offer students to gain valuable experience in basic, translational and clinical research.”

Tags: Department of Orthopaedics, Dr. Dimitrios Kouroupis, Dr. Francis Hornicek, Dr. Thomas Best, osteoarthritis