Project Overview
Currently, many people in the United States are living longer, healthier lives, enjoying the benefits that come with first-rate healthcare and nutrition. However, a consequence of living longer is an increased risk for certain diseases, including osteoarthritis (OA). OA is the result of cartilage degradation in the joints, which leads to increased friction between bones; this friction causes pain and joint immobility. More than 52.5 million adults in the United States currently suffer from OA, and the number of cases is projected to grow as the population ages (Lawrence et al., 2008). There is currently no cure for OA, and many patients with the disease must endure chronic pain. The most common OA treatments address symptoms of OA instead of targeting the underlying causes of the disease. As a result, many of these treatments only provide temporary pain relief, and the disease continues to progress (Mayo Clinic, 2014).
A potential new treatment for OA involves the use of extracellular vesicles (EVs) as delivery vehicles. EVs are vital components in cell-to-cell communication within the body. They are able to transport a number of different molecules, including microRNA (miRNA) which prevent the translation of specific mRNA sequences thereby downregulating gene expression. Utilizing proteins on their cell membranes, EVs can target and deliver cargo to specific cells such as chondrocytes, the cells that maintain articular cartilage (György, Hung, Breakefield, & Leonard, 2015). Extracellular matrix (ECM) is the main constituent of articular cartilage, and as a result ECM maintenance is closely related to articular cartilage health. (Sophia Fox, Bedi, & Rodeo, 2009). In a joint affected by osteoarthritis, ECM is degraded, which negatively affects joint function and health. Promoting the regeneration of healthy ECM proteins by controlling the cargo delivered by EVs to chondrocytes is a potentially effective treatment for OA. It follows that the purpose of this study is to manipulate EV cargo to promote cartilage tissue regeneration for the treatment of OA.
Research Questions & Hypotheses
We aim to develop an EV-based OA treatment that utilizes a practical and effective cell source as well as engineered miRNA cargo.
Our proposed research questions and hypotheses are as follows:
Research Questions:
Banner picture courtesy of Dr. John Fisher, a professor in the UMD Bioengineering Dept.
A potential new treatment for OA involves the use of extracellular vesicles (EVs) as delivery vehicles. EVs are vital components in cell-to-cell communication within the body. They are able to transport a number of different molecules, including microRNA (miRNA) which prevent the translation of specific mRNA sequences thereby downregulating gene expression. Utilizing proteins on their cell membranes, EVs can target and deliver cargo to specific cells such as chondrocytes, the cells that maintain articular cartilage (György, Hung, Breakefield, & Leonard, 2015). Extracellular matrix (ECM) is the main constituent of articular cartilage, and as a result ECM maintenance is closely related to articular cartilage health. (Sophia Fox, Bedi, & Rodeo, 2009). In a joint affected by osteoarthritis, ECM is degraded, which negatively affects joint function and health. Promoting the regeneration of healthy ECM proteins by controlling the cargo delivered by EVs to chondrocytes is a potentially effective treatment for OA. It follows that the purpose of this study is to manipulate EV cargo to promote cartilage tissue regeneration for the treatment of OA.
Research Questions & Hypotheses
We aim to develop an EV-based OA treatment that utilizes a practical and effective cell source as well as engineered miRNA cargo.
Our proposed research questions and hypotheses are as follows:
Research Questions:
- How does cell source affect the therapeutic potential of EVs for OA treatment?
- How can EVs be actively loaded with therapeutic miRNAs to amplify their therapeutic activity?
- Hypothesis: Cell source and miRNA content of EVs dictates their therapeutic potential and can be measured by observing ECM protein generation and OA pathology progression in chondrocytes. SFBs, BM-hMSCs, and UC-hMSCs are potential cell sources that release therapeutic EVs because of their ability to influence chondrocyte bioactivity; miRNA-140, miRNA-27a, miRNA-27b, LNA-antimiRNA-34, and miRNA-222 are known to play a role in cartilage regeneration, so they have potential as therapeutic cargo.
Banner picture courtesy of Dr. John Fisher, a professor in the UMD Bioengineering Dept.