02078: Development of a Regenerative Medicine Technique to Treat Cartilage Disorders in Dogs
Grant Status: Closed
Osteochondrosis is a common and debilitating disease affecting large, athletic dogs. Osteochondrosis is caused by abnormal endochondral ossification, the process by which growth plate cartilage adjacent to joint surfaces transitions from cartilage to bone. The result is excessively thickened cartilage that partially or completely separates from surrounding bone. Cartilage separation exposes the joint to underlying bone and creates a large loose body, termed a joint mouse, within the joint. Surgical or medical treatment results vary widely based on the affected joint, size of the osteochondrosisdefect, and intended purpose for each dog. Treatment options for osteochondrosishave remained essentially unchanged for decades. Tissue engineering represents a promising treatment alternative for dogs suffering from OC. Dr. Saunders believes the key to successful tissue engineering involves generation of regenerative osteochondral plugs, or ROPs. ROPs are tri-layered cylindrical plugs composed of hydrogels seeded with adult mesenchymal stem cells (MSCs). Each ROP layer is composed of materials that closely mimic specific zones of the joint and adjacent bone. ROP layers are bioactive, directing encapsulated MSCs to differentiate into specific tissues to more efficiently restore normal joint anatomy. Dr. Saunders will optimize the materials used to generate ROP layers and will determine if MSCs from tissue lining the joint (synovium) or inner cavity of bones (bone marrow) more effectively reconstruct native cartilage, transitional tissue, or bone. This work represents an important advance in canine regenerative medicine and is highly applicable to dogs with osteochondrosisor other common joint ailments such as osteoarthritis.
Bearden, R. N., Huggins, S. S., Cummings, K. J., Smith, R., Gregory, C. A., & Saunders, W. B. (2017). In-vitro characterization of canine multipotent stromal cells isolated from synovium, bone marrow, and adipose tissue: a donor-matched comparative study. Stem Cell Research & Therapy, 8(1). https://doi.org/10.1186/s13287-017-0639-6
Diaz‐Rodriguez, P., Erndt‐Marino, J. D., Gharat, T., Pinto, D. J. M., Samavedi, S., Bearden, R., … Hahn, M. S. (2018). Toward zonally tailored scaffolds for osteochondral differentiation of synovial mesenchymal stem cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 1–11. https://doi.org/10.1002/jbm.b.34293
Gacasan, E. G., Sehnert, R. M., Ehrhardt, D. A., & Grunlan, M. A. (2017). Templated, Macroporous PEG-DA Hydrogels and Their Potential Utility as Tissue Engineering Scaffolds. Macromolecular Materials and Engineering, 302(5), 1600512. https://doi.org/10.1002/mame.201600512
Gharat, T. P., Diaz-Rodriguez, P., Erndt-Marino, J. D., Jimenez Vergara, A. C., Munoz Pinto, D. J., Bearden, R. N., … Hahn, M. S. (2018). A canine in vitro model for evaluation of marrow‐derived mesenchymal stromal cell‐based bone scaffolds. Journal of Biomedical Materials Research Part A, 106(9), 2382–2393. https://doi.org/10.1002/jbm.a.36430
Help Future Generations of Dogs
Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.