Knee joints are composed of different tissues including cartilage, ligaments and meniscus. The meniscus has a role in stabilizing the knee joint and protects cartilage during walking and sporting activities. Damage to meniscus through activity or age-related degeneration are major factors in the development of whole joint diseases like osteoarthritis. This condition is the number one cause of disability in the United States, affecting over 27 million people in the USA alone. Despite substantial developments in surgical techniques, instrumentation, and orthopaedic devices, long-term clinical outcomes are not satisfactory. We propose a multidisciplinary approach by combining our knowledge of human meniscus biology, expertise in stem cell biology and specialized support structures (scaffolds) and tissue regeneration (engineering) to repair torn/damaged meniscus tissue and to regenerate a partial section of meniscus tissue. The objectives include the selection of the appropriate stem cell type, refinement of scaffold with optimal biomechanical properties, and construction of the net shape to aid in surgically implanting the generated meniscus tissue to survive in a knee joint of a live animal (rabbit and minipig). The ideal combinations of cells and scaffold will be prepared for human clinical trials. Successfully treating meniscal injury and deficiency at an early stage will reduce the incidence of secondary osteoarthritis and lessen the burden on healthcare.
Statement of Benefit to California:
The menisci are key components of the normal knee joint and loss of a meniscus invariably leads to irreversible joint damage and secondary osteoarthritis (the annual cost of treating osteoarthritis exceeds $120B in the US). Due to lack of intrinsic healing, the standard treatment for meniscal injury is surgical resection which eventually leads to secondary osteoarthritis.
Biomimetic meniscal repair that replicates biological, biochemical and biomechanical functions and addresses the major weaknesses in current treatment is more likely to succeed.
This application addresses an unmet medical need that, if successfully developed and made available to patients, will represent a significant improvement upon the current standard of care. Successfully treating meniscal injury and deficiency at an early stage will reduce the incidence of secondary osteoarthritis and lessen the burden on healthcare.
This grant proposal falls under the mission statement of the CIRM for funding innovative research. A stem cell based approach for treating meniscal lesions is not represented in CIRM’s current Translation Portfolio. This proposal will also expand the field in a new direction and integrate multidisciplinary methods. If successful, this will further validate the significance of the CIRM program and will help maintain California's leading position at the cutting edge of biomedical research.