I-CORPS: Stem Cell-Derived Scaffolds For Spinal Fusion And Maxillofacial Bone Repair
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abstract
The broader impact/commercial potential of this I-Corps project addresses the treatment of musculoskeletal disease and injury, which are among the most common reasons patients seek medical treatment. These procedures arise from treatment of traumatic injury, congenital defects, tumor resection, and joint replacements. Bone fractures comprise a majority of these disorders with 6.2 million fractures. However, it is estimated that up to 10 percent of these bone defects are associated with improper healing. Without the aid of a bone graft material, these defects result in low structural integrity and potentially result in amputation. The gold standard of treatment relies on using bone from the patient as a graft. The technology under developed by this project, extracellular matrix derived from osteogenic stem cells, offers a bone graft material with equivalent healing properties to a patient''s bone graft without the potential chronic pain and risk of infection associated with the harvesting a bone graft. From a scientific perspective, this project represents a disruptive change to all cell-derived matrix technologies, and as a result has the potential to drive innovative tissue engineering-based solutions to regenerate other tissues. This I-Corps project aims to generate an osteogenic bone graft material derived from cultured mesenchymal stem cells (hMSCs). The technology coaxes hMSCs to differentiate into an intermediate osteogenic phenotype that can be used generate extracellular matrix that mimics the primitive stroma deposited during embryological bone development and during bone repair in adults. When purified from the cells, this material exhibits remarkable biocompatibility and significantly increases retention of engrafted hMSCs, with far greater binding capacity than commonly employed bone substitutes. Importantly, these properties accelerate bone repair and spinal fusion in animal models. Methods have been developed to produce and harvest this matrix from hMSCs derived from induced pluripotent stem cells that can be theoretically expanded indefinitely, hence it is possible to now produce large amounts of osteogenic matrix with reliable properties. Further, these cells are actually able to produce matrix in much higher quantities than that produced by bone marrow-derived hMSCs. This is a platform technology to harvest and combine this matrix with surgical collagen sponge or other suitable scaffolds as a replacement for currently used allogenic scaffolds.
