Osteoarthritis (OA) is a disease that has significant individual, social, and economic impact worldwide. Although many etiologies lead to the eventual development of OA, one potentially treatable cause is the acute articular cartilage (AC) injury. These injuries are common and have a poor inherent healing capacity, leading to the formation of OA. In an effort to repair AC injuries several treatment strategies have been developed but none have proven completely successful.
Studies examining AC tissue-engineering strategies have suggested that those with the most potential for success involve the introduction of autogenous or allogenous cells to the site of injury. These strategies are designed to encourage creation of a matrix with the appropriate characteristics of normal AC. However, development of a completely successful repair method has proven difficult because the biomechanical properties of normal AC are not easy to replicate, a cell source with the appropriate functional characteristics has not been optimized, and the problem of effective incorporation of a repair construct into the host tissue remains unresolved.
In an effort to more fully understand the cartilage repair process, this work first focused on the development and utilization of an in vitro human explant model of AC to study the ability of seeded human chondrocytes to integrate into an AC defect. Further work elucidated the gene expression patterns of cultured adult human chondrocytes and human mesenchymal stem cell (MSC)-derived chondrocytes.
Results from this work determined that cultured human chondrocytes were able to adhere to articular cartilage defects in a viable in vitro explant model and produce a matrix containing collagen type II. However, further work with the in vitro expanded chondrocytes revealed that these cells have increased expression of collagen type I which promotes the formation of a less durable fibrocartilagenous tissue. This unfavorable expression persisted despite placing the chondrocytes in an environment favoring a chondrocytic phenotype. Further work with MSC-derived chondrocytes demonstrated a similar and unfavorable production of collagen type I. This work represented an important first step towards a treatment for acute AC lesions but it is clear that further work to optimize the culture microenvironment is still required. / Experimental Surgery
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1109 |
| Date | 06 1900 |
| Creators | Secretan, Charles Coleman |
| Contributors | Jomha, Nadr (Department of Surgery), Bagnall, Keith (Department of Surgery), Simmonds, Andrew (Department of Cell Biology), Raso, Jim (Department of Surgery), Matyas, John (Department of Veterinary Medicine, University of Calgary), Jomha, Nadr (Department of Surgery), Bagnall, Keith (Department of Surgery), Simmonds, Andrew (Department of Cell Biology), Churchill, Thomas (Department of Surgery) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 1135790 bytes, application/pdf |
| Relation | Effects of introducing cultured human chondrocytes into a human articular cartilage explant model. Secretan C, Bagnall KM, Jomha NM. Cell Tissue Res. 2010 Feb;339(2):421-7. Epub 2009 Dec 12., The development of osteoblasts from stem cells to supplement fusion of the spine during surgery for AIS.Jiang H, Secretan C, Gao T, Bagnall K, Korbutt G, Lakey J, Jomha NM. Stud Health Technol Inform. 2006;123:467-72. |
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