Toward development of a potassium (K+)-based intra-articular injection for osteoarthritis treatment
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Authors
Erndt-Marino, Joshua Dean
Issue Date
2018-05
Type
Electronic thesis
Thesis
Thesis
Language
ENG
Keywords
Biomedical engineering
Alternative Title
Abstract
Osteoarthritis (OA) is characterized by a slow progression of cartilage erosion driven in part by a cascade of inflammatory mediators produced from an activated synovium and the cartilage itself. Chondrocytes lose their capacity to maintain a healthy cartilage extracellular matrix as they transition from an anabolic, healthy phenotype to a catabolic, hypertrophic phenotype. Activated synovial macrophages contribute to the chondrocyte phenotype shift and subsequent cartilage degradation through the secretion of pro-inflammatory molecules. Currently, there is not a single effective disease modifying treatment that can intervene in this degradative cascade. The goal of this work is to develop an intra-articular (IA) injection treatment that targets these two aberrant cell phenotypes through depolarization of the cells’ transmembrane potential (Vmem). Increasing the extracellular potassium (K+) concentration is a simple way to depolarize Vmem. In theory, a K+-based IA solution would be inexpensive, widely available, easy-to-implement, and able to alleviate long-term storage concerns associated with other potential treatments such as stem cells or protein-based pharmaceuticals.
This thesis focuses on initial, in vitro proof-of-concept studies designed to demonstrate the therapeutic potential a K+-based IA injection treatment for OA. Specifically, addition of K+ gluconate into culture media induces favorable changes in both osteoarthritic chondrocytes and interferon-gamma stimulated macrophages (M(IFN)). Furthermore, short-term stimulation (1 day) with K+ gluconate elicits prolonged beneficial responses in M(IFN) after 5 days despite the continued presence of IFN. The macrophage response noticed with K+ gluconate is not observed with either a clinically utilized IA injectable (methyl-prednisolone acetate - a corticosteroid) or a cell-based (human mesenchymal stem cell) injectable. Future work for this project will move towards in situ and in vivo studies.
This thesis focuses on initial, in vitro proof-of-concept studies designed to demonstrate the therapeutic potential a K+-based IA injection treatment for OA. Specifically, addition of K+ gluconate into culture media induces favorable changes in both osteoarthritic chondrocytes and interferon-gamma stimulated macrophages (M(IFN)). Furthermore, short-term stimulation (1 day) with K+ gluconate elicits prolonged beneficial responses in M(IFN) after 5 days despite the continued presence of IFN. The macrophage response noticed with K+ gluconate is not observed with either a clinically utilized IA injectable (methyl-prednisolone acetate - a corticosteroid) or a cell-based (human mesenchymal stem cell) injectable. Future work for this project will move towards in situ and in vivo studies.
Description
May 2018
School of Engineering
School of Engineering
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY