Grant: Project Grant

Osteoarthritis (OA) is a chronic disease, affecting 14% of the Canadian population and 8% of the global population. There is no treatment for OA, and current therapies are largely palliative. There is an urgent need for disease-modifying strategies that address the multifactorial characteristics of OA, including cartilage degeneration, abnormal bone remodelling, and joint inflammation. TGF-beta signalling is a prominent pathway that gets dysregulated in OA and drives pathological phenotypes across joint tissues. Its modulation through gene therapy holds promise in treating OA. Using nanoparticles (NPs) to deliver genetic therapies improves their retention and efficacy. Extracellular vesicles (EVs) are biological NPs released by cells that have gained prominence in drug delivery as they have innate biocompatibility and additional therapeutic effects, such as anti-inflammation and tissue regeneration. However, challenges in scalability, among other limitations, continue to hinder their clinical translatability. Nanoghosts (NGs) are another class of NPs artificially made by downsizing cell membranes into EV-like structures. They inherit important bioactive components from the parent cell, making them as biocompatible as EVs while offering improved scalability and engineering prospects. We have recently shown that NGs from mesenchymal stem cells (MSC-NGs) intrinsically improve osteogenic outcomes. Our preliminary results showed that MSC-NGs are tolerated in mice and can enhance the rate of bone healing. Additionally, MSC-NGs have been shown by us and others to have desirable anti-inflammatory effects, as well as positive regulation of cartilage regeneration. According to these findings, we stipulate that loading MSC-NGs with gene therapy that modulates TGFbeta signalling and targeting them to specific joint tissues, such as cartilage and bone, will generate a multifaceted, synergistic therapeutic effect that can potentially improve clinical outcomes for OA patients.