Title:
Engineering an improved cartilage repair strategy combining cells and ECM-derived materials
Engineering an improved cartilage repair strategy combining cells and ECM-derived materials
Author(s)
Burnsed, Olivia A.
Advisor(s)
Guldberg, Robert E.
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Abstract
Osteoarthritis (OA) is the leading cause of disability in the US. The avascularity, low cellularity, and slow proliferation of chondrocytes as well as joint inflammation all limit the regenerative capacity of cartilage. Cell therapies, such as autologous chondrocyte implantation (ACI), offer promising options for treating cartilage lesions, but the inability to expand chondrocytes to sufficient numbers without adversely affecting their phenotype remains a significant problem. ACI is not indicated for OA or other inflammatory diseases, likely due to the inflammatory environment cells are exposed to upon implantation since multiple inflammatory mediators are involved in OA. Anti-inflammatory therapies with single molecular inhibitors are unable to modulate the complex inflammatory environment in OA. Thus, novel therapies capable of modulating multiple signaling pathways and cell types are an attractive alternative to address OA inflammation. Therefore, the objective of this proposal was to engineer an improved cartilage repair strategy combining cells and ECM materials to address problems with both cartilage repair and OA-associated inflammation. Decellularized cartilage microcarriers were developed to expand chondrocytes while retaining their phenotype. We also characterize the effects of aggregation, culture conditions, and donor variability on mesenchymal stem cell (MSC) immunomodulation of OA. To this end, we quantified MSC paracrine factor production, suppression of activated synoviocyte inflammation, and therapeutic efficacy in the rat medial meniscal transection (MMT) model of OA. Furthermore, we investigated the interaction between MSCs and human amniotic membrane and the influence of cell-cell and cell-ECM therein on the modulation of inflammation, both in vitro and in vivo. Overall, this work broadens current understanding of cartilage tissue engineering and immunomodulation via ECM and stem cell-based therapies, providing valuable information that can be used to develop strategies to improve efficacy of osteoarthritis treatments.
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Date Issued
2017-11-13
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Text
Resource Subtype
Dissertation