Autologous Tolerogenic Dendritic Cell for Improving Post-Traumatic Osteoarthritis Therapy
Abstract
Osteoarthritis (OA) is a chronic joint disease caused by progressive cartilage degeneration that is often accompanied by joint pain, stiffness, and disability. The clinical burden of OA affects one in five Americans and results in activity limitations for one in ten, and it costs more than $128 billion dollars per year in work losses and disease management. Degenerative OA occurs most commonly in adults older than 65 years, whereas post-traumatic OA (PTOA) represents a different pathology and may occur in a younger population. Rates of PTOA are five times higher and affected ages are lower in active military Service members and Veterans than in civilian populations due to the nature of tactic athletics that are closely associated with joint injuries including acute ligament sprain or chronic ligamentous instability or both. PTOA is among the most common causes of disability in Service members who are medically retired or separated from the military. The proposed study is specifically designed to explore a novel treatment method for PTOA, a designated topic area, which significantly contributes to the rapidly growing OA population in both the military and the general population. Since cartilage and ligaments have a lack of regeneration ability, regenerative mesenchymal stem cell (MSC)-based therapeutic methods have been extensively studied. Researchers have paid a great attention to utilizing allogenic MSC (cells from healthy individuals) because of its immune-privileged characteristics, which enable its application broadly to the other patients. Although the “off-the-shelf” concept of allogenic MSC therapy makes it more affordable and feasible, the major challenge of allogenic MSC treatment is to improve their survival by protecting them from host immune rejection. Specifically, despite their “immune-privileged” nature, allogenic MSCs are indeed recognized as foreign cells and ultimately rejected by the host immune system at some level. Therefore, as allogenic MSCs are ultimately eliminated by the host immune system, their utility declines by limiting their potential for long-term persistence and their capacity to promote more effective cartilage restoration. Because inflammatory conditions at the site of PTOA constantly give signals to deteriorate cartilage and to promote a response to allogenic MSCs, the long-term suppression of inflammatory cells is a key aspect for successful cartilage restoration. It is now well known that tolerogenic dendritic cells are in a fundamental position to be exploited to suppress inflammatory cell activation and proliferation. In agreement, clinical application of tolerogenic dendritic cells has resulted in effective immune suppression for patients with a solid organ transplantation. Therefore, in mice model mimicking human PTOA, the role of tolerogenic dendritic cells will be assessed, for the first time, for improving allogenic MSC-based cartilage repair through immune suppression. If successful, this novel combinatory cell-based therapy would deliver a great enhancement of therapeutic efficacy of allogenic MSC and provide a hope for more durable cartilage restoration therapy to both military and general PTOA patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010038
Entities
People
- Seunghwan Lim
Organizations
- United States Army