Stem cells for treating focal cartilage injury

Funding Type: 
Early Translational II
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Arthritis is a disabling condition that afflicts 6 million Californians and costs our state nearly $32 billion a year in healthcare and lost wages. Yet arthritis remains an unmet medical need and its overall impact will increase steadily given that more of the population is aging and that the inability to maintain an active lifestyle has severe consequences for many aspects of health. Sixty million Americans are projected to have arthritis by 2020. In the absence of effective 'arthritis drugs,' joint replacements offer some relief but have limited durability and are unsuitable for young patients. Other treatments that try to repair cartilage damaged prior to arthritis, such as microfracture of underlying bone or cartilage cell transplantation, fail to restore native mechanical and biological properties of the joint and do not avoid disease progression. For preventing arthritis, stem cells have obvious appeal, but directing them to synthesize a desirable cartilage matrix has proven challenging.

We have made a fundamental advance in overcoming limitations to the use of stem cells for cartilage repair. We have developed a construct in which human mesenchymal stem cells (MSC) are grown alongside highly instructive juvenile cartilage cells. These cells are arranged in bilaminar cell pellets (BCPs), and embedded in an FDA-approved biomaterial. BCPs synthesize abundant articular cartilage matrix, adapt to the unique environment of the joint, and resist inflammation. The biomaterial retains the BCPs at the defect site while, over time, BCPs secrete cartilage matrix to replace the biomaterial. We propose a focused plan to optimize BCP interactions with the biomaterial; demonstrate feasibility, safety, and efficacy; standardize cell isolation, and create a product development plan. Our goal is to accelerate translation of this novel stem cell-based therapy to provide an early intervention for preventing and treating arthritis.

With support of a CIRM Disease Team Planning Grant, we assembled an outstanding team of experts from Academia and Industry with the experience and motivation to achieve our goal. The team leader is Director of an industry-collaborative center and an Orthopaedic Biomechanics Laboratory, and a pioneer of protocols for turning stem cells into cartilage. Our Academic partners bring world-recognized leadership in stem cell and skeletal biology, and clinical expertise in orthopaedic surgery, including past clinical evaluations of other cell-based therapies. Our Industry partner has established products for clinical applications, and will contribute expertise in cell sourcing, manufacturing, and regulatory processes. By combining the creativity and innovation of Academia with the pragmatic focus of Industry, our team is poised to meet the challenge of generating pre-clinical data that will support future IND-enabling studies.

Statement of Benefit to California: 

Approximately 6 million adults in California, or 27% of the population, have some form of arthritis. This disease costs California nearly $32 billion each year, with an estimated $23.2 billion spent on direct medical care and $8.3 billion due to lost wages. The Centers for Disease Control and Prevention projects that 60 million people nationwide will have arthritis by 2020. Osteoarthritis is a disabling disease that limits the ability to engage in the regular physical activity that prevents obesity, diabetes, and cardiovascular disease. Consequently, successful development of improved arthritis therapies will benefit a significant portion of the California population. Additionally, we anticipate that the management structure of this program along with the cell/matrix technologies can ultimately be applied to a host of other musculoskeletal diseases such as back pain, osteoporosis, and fracture repair.

In addition to the health of Californians, cell based therapies for arthritis and other musculoskeletal conditions provide a huge commercial opportunity for California industry. Credit Suisse has estimated that the growth potential for the orthopaedic industry focused on hip and knee treatment is positive, with projected global sales expanding from $9.6 billion in 2006 to $13 billion in 2011. The orthobiologic market that includes regenerative technologies currently accounts for roughly 12% of the worldwide orthopaedic implant market and is the fastest growing segment, at 20% annually.

Both our subcontractors (PCT and ISIS) will directly benefit from this effort. Clearly their economic success will provide employment opportunities for Californians, tax revenue for the state, and help maintain California as a world leader in biotechnology research and development.

This work also aids the research enterprise of California universities by augmenting our competitiveness for NIH funding. This, in turn, brings the brightest scientific talent to the state, fuels innovation, and ensures continued California leadership in the biotech industry.

Given the significant unmet clinical need, market opportunity, and rapidly evolving technologies, we anticipate that stem-cell based therapies for arthritis will be realized in the next 4 to 8 years. The CIRM Early Translational Research Award can assure that this important therapy with the potential to prevent the progression of osteoarthritis is developed in California.