Embryonic Stem Cell-Derived Chondroprogenitor Cells to Repair Osteochondral Defects

Funding Type: 
Disease Team Therapy Development III
Grant Number: 
DR3-07078
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Arthritis is a common disease and increases with age. The annual cost of treating arthritis in the US is estimated to be over $200B in 2013. Over a million joint replacements are performed in the US alone for end-stage arthritis. However, for younger patients with severe arthritis or impending arthritis there is no treatment that can prevent, cure, or even slow the progression of this disease. In this proposal we target the repair and regeneration of knee cartilage and underlying bone defects (lesions) that if are left untreated are a major factor in contributing to early osteoarthritis in patients less than 55 years of age. Our approach is to advance a third-generation cell therapy by combining stem cells with a natural hydrogel scaffold to support the repair cartilage and bone defects. This application proposes a multicenter collaboration among investigators at Scripps Health, Scripps Research Institute, Sanford/San Diego Consortium for Regenerative Medicine, and City of Hope. Each center contributing key expertise toward this project effectively span the translational bridge between basic science and the clinic. We have assembled a development team consisting of translational scientists; physicians with expertise in multi-center clinical trials; four adult knee reconstruction surgeons; stem cell biologists; three members of the FDA Cellular, Tissue and Gene Therapies Advisory Committee; a rheumatologist; a musculoskeletal radiologist; a biostatistician; and a biomechanist. We propose to conduct the following “investigational new drug” IND-enabling activities. Manufacture and Characterize cell lines and scaffold under clinically approved conditions Conduct preclinical proof of concept, dosing, and mechanism action studies Two animal model species will be used following Guidance for Industry. Small (rabbit) and large animal (goat) models based on anticipated reaction of these animal to human cells, as well as the biological and biomechanical relevance, and FDA recommendations. As well, goat knees more closely approximate the scale of human knees. This will facilitate accurate assessment of the cell/scaffold dose and route of administration. Conduct Safety Studies In our rabbit and goat animal models, we will study short-term, long-term, and delayed-onset toxic or adverse responses to the implanted cells. We will examine the knee and the entire body for cell death, tumor formations and durability of the regenerated tissue, and whether the regenerated tissue is normal. If this approach is successful this will be the first-in-man embryonic stem cell-based treatment of an orthopaedic disease that has challenged repeated attempts over the last 400 years.
Statement of Benefit to California: 
Arthritis is a common disease and increases with age. The annual cost of treating arthritis in the US is estimated to be over $200B in 2013. Over a million joint replacements are performed in the US alone for end-stage arthritis. However, for younger patients with severe arthritis or impending arthritis there is as yet no treatment that can prevent, cure, or even slow the progression of this disease. In this proposal we target bone and cartilage defects that are a major factor in contributing to early osteoarthritis in patients less than 55 years of age. Our approach is to advance third-generation cell therapy by constructing scaffolds that are seeded with chondroprogenitor cells programmed to undergo differentiation into bone and cartilage cells. This proposal falls under the mission statement of CIRM for funding innovative research. A stem cell based approach for treating articular cartilage defects in not represented in CIRM’s current portfolio. If successful this will be the first-in-man embryonic stem cell based treatment of an orthopaedic disease that has challenged repeated attempts over the last 400 years. This will further validate the significance of the CIRM program and help maintain California’s leading position at the cutting edge of biomedical research

© 2013 California Institute for Regenerative Medicine