The Joint Transplantation Program
Part of the McCaig Institute for Bone and Joint Health, the Joint Transplantation Program uses live bone and cartilage from young donors to repair damaged bone and cartilage in the shoulders and knees of patients under the age of 60. Using tissue from young cadaveric donors allows surgeons to avoid using artificial materials that may wear out and need to be replaced. “Most of these patients have no other option,” says Tanja Harrison, Coordinator of the Joint Transplantation Program at the U of C. “They’re too young to have total joint replacements that typically wear out within 10 – 15 years and they have failed other traditional options such as microfracture. So this surgery gives patients an alternative to living with pain and disability with the intention of preventing, or at least delaying, the need for an artificial joint replacement.”
Surgeons take donor cartilage matched to the precise size and location of the damaged tissue, test and prepare it, remove the damaged tissue of the recipient, and transplant the new, viable tissue in its place. Joint transplants have been done internationally since the ‘80s, but have had varying success rates because of struggles to keep donor tissue viable for longer than 72 hours. That isn’t long enough to do all the compatibility and safety tests required, some of which can take 7 – 10 days, so the alternative has been to freeze the tissue, which can result in higher failure rates.
In 2006, researchers with the Joint Transplantation Program developed a new way of keeping donor tissue viable for up to 30 days using hypothermic storage (4°C), which allows them to confirm the safety and viability of the tissue. “At this point, we are able to confirm a viability of greater than 90 percent,” says Harrison. “We are the only place in the world that uses this preservation technique.” The Program is now able to transfer tissue from one donor to hospitals in Edmonton and Banff for transplants at multiple sites.
“With this research project, we’ve established that biologic resurfacing of cartilage injuries is not only possible, but with our preservation technique, it’s highly effective,” says Dr. Scott Timmermann, Director of the Joint Transplantation Program. The next steps are to take this research and turn it into a standard practice of care throughout the province and beyond. “The goal of the Program was to translate validated basic science into clinical practice, and I think we’re very close to that,” says Timmermann. “At this point, its only limitations are availability of tissue – that is our Achilles heel.”
The U of C team collaborates with the Southern Alberta Tissue Program to maximize the donor tissue they receive. Last October the Program reached a milestone - four patients received transplants from just one donor.
Joint transplants aren’t for everyone, cautions Dr. Scott Timmermann, Director of the Joint Transplantation Program at the U of C. Participants in the Program are referred by their physician. The following are the criteria for taking part in the research program:
- Focal injuries of the cartilage involving the distal femur (knee) or proximal humerus (shoulder) between 10-35 mm in size
- Larger bulk knee injuries, for example tibial plateau fractures
- Skeletally mature patients between the ages of 16-60
- Other therapies have been tried and failed
How can we IMPROVE THE TREATMENT of the disease?
Patients Weigh-in on Rheumatoid Arthritis and Crohn's Disease Treatment
Rheumatoid Arthritis and Crohn's are both chronic immune-mediated diseases that share similar treatments. Choosing the right treatment can be difficult, as treatments differ in their benefits, potential side effects and route of administration. Patient preferences should inform how to balance the benefits and potential risks, but currently, treatment recommendations for both conditions are made primarily based on research evidence alone. Glen Hazelwood, MD PhD is developing a novel method to help inform patient-centered treatment approaches to improve the lives of patients with both Crohn's disease and rheumatoid arthritis. He was just granted a highly competitive CIHR catalyst grant for $99,744 sponsored by the Drug Safety and Effectiveness Network (DSEN) and the Strategy for Patient-Oriented Research (SPOR) entitled "Bayesian models for synthesizing randomized controlled trials and patients¹ preferences for treatment options in early rheumatoid arthritis and Crohn's disease".
Inventions that Impact Surgery
Carolyn Anglin, PhD has created an innovative device for use by orthopaedic surgeons during total joint replacement. The device allows surgeons to better identify the angle at which the bones are cut. This has significantly improved the precision of these procedures and will likely contribute to increased functionality and longevity of the implant.
Exploring Non-surgical Solutions
In June of 2013, the Orthopaedic Trauma Research group began recruiting for a clinical trial that aims to help patients suffering from elbow fractures or dislocations. Elbow injuries such as these are frequently associated with post-traumatic loss of motion. Up to 12% require additional surgery, regardless of physiotherapy during the healing process. Earlier preclinical laboratory studies suggest that Ketotifen, a commonly used and widely available drug for treatment of asthma, could potentially reduce elbow joint stiffness after injury.
In this double-blinded study, where neither the patients nor the investigators know if the subject is taking a placebo or the drug, patients will take Ketotifen orally for six weeks while attending regular follow-ups to monitor range or motion and healing progress. Recruitment of subjects will be continuing until the end of 2014.
Restoration of Function in Rheumatoid Arthritis
The Arthritis Society has awarded Cheryl Barnabe, MD and Steve Boyd, PhD $333,989 for their study “Erosion Healing in Restoration of Function in Rheumatoid Arthritis”. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), a sensitive imaging technique with excellent bone image resolution, the researchers will investigate the effect of treatment on bone structure in rheumatoid arthritis, and specifically whether erosion healing can be demonstrated. A feature of damage in rheumatoid arthritis is erosions, which can be described as holes in the bone near the joint that cause hand dysfunction and disability. A controversial topic in rheumatology is whether these erosions are a permanent condition or if new bone can be deposited in the erosion and fill the defect, restoring the joint to its normal architecture. This imaging work will be supplemented with a determination of how these findings correlate with objective measures of hand function.
The Study of Stem Cells to Manage Degenerative Disease
A few years ago, a Japanese group showed that mature adult skin cells could be genetically reprogrammed into embryonic stem cell-like cells. This advancement was significant since patient-specific pluripotent stem cells could be created without the destruction of an embryo. However this reprogramming technique relied on the use of cancerous agents and was highly inefficient, requiring one million adult cells to generate one stem cell. In May 2012, Derrick Rancourt, PhD and Roman Krawetz, PhD reported an innovative technique to generate millions of reprogrammed stem cells, without the use of cancerous agents. Using suspension bioreactors, stem cells can now be generated safely at the numbers needed for treating patients.
This discovery was significant and has brought us one step closer to realizing the dream of creating new clinical therapies for patients. To see the video, click here.
Rancourt was awarded a CFI Leaders Opportunity Fund award of $167,304 to help develop his new lab in the McCaig Institute. His proposal entitled “Bioreactor Derived Induced Pluritpotent Stem Cells for Diagnostic and Therapeutic Application” will explore how stem cells are a valuable resource in identifying novel treatments for someone suffering from a degenerative disease, such as osteoarthritis. Through the CFI funding of cell culture suites and bioreactors systems, Rancourt will explore new ways to improve the management of degenerative disease by targeting and refining how stem cells are generated and used.
Keeping Joints Lubricated
Tannin Schmidt, PhD has discovered that the lubricating properties of synovial fluid are altered after joint injury but they recover over time. His team is investigating whether this temporary loss in lubrication is responsible for later development of osteoarthritis, and he is developing ways to maintain joint lubrication in order to potentially avoid disease onset altogether.
What Clues Can We Draw from Super-healer Mice for Cartilage Repair?
Roman Krawetz's, PhD research will use a “super mouse”; a mouse species with self-repairing cartilage (a tissue that in “normal” mammals and humans does not self-repair) to study how cells affect the ability to self-repair cartilage. Krawetz is interested in studying progenitor cells; cells similar to stem cells in that they have the ability to turn into many different types of cells and can be pushed to become a specific “target” type of cell. He will be studying whether these “super-healer” mice have the ability to repair cartilage as a result of changes to the behavior of these progenitor cells, and whether there are other factors in addition to cell behavior that affect repair such as the inflammatory response after injury.
The results of this study as well as future experiments will define a research program that aims to develop new tissue engineering and regenerative medicine solutions for the repair of tissues that currently are unable to heal themselves.
Roman Krawetz was successful in his grant application to the Canadian Institute of Health Research Clinical Investigation Committee, securing five years of funding totaling $731,707 for his new clinical investigation.