Endogenous and Exogenous Pericytes in the Pathobiology and Treatment of Osteoarthritis
Abstract
Topic Area: Arthritis Osteoarthritis (OA) affects over 50 million individuals, costing over $180 billion annually and representing one of the leading causes of disability in the United States. OA is also very common among military Service men and women, resulting in high medical discharge, lowered return to duty among active Service men, and high disability among Veterans. The surgical treatment of OA is costly and poses relatively high risks to the patient. In aggregate, more cost-effective, efficacious, and safer treatments for OA are urgently needed. Mesenchymal stem/stromal cells (MSC) have long been recognized to have robust regulatory effects on the immune system. The vascular wall is a source of multipotent MSC, and the microvascular “pericyte” represents the most commonly studied perivascular MSC. Pericytes have known biological roles in immune regulation. For example, implanted pericytes quiet inflammation in cardiac ischemia (heart attack) or after skeletal muscle injury. However, the natural immune regulatory functions of pericytes within the joint space are entirely unknown. The present Discovery Award application seeks to explore the entirely novel hypotheses that: (1) joint space pericytes may exert protective/immunomodulatory effects in OA and (2) non-invasive injection of purified pericytes will improve OA disease progression. Aim 1: Develop and evaluate a post-traumatic osteoarthritis model (PTOA) within pericyte reporter mice. Here, we will utilize a transgenic reporter animal model in a mouse model of PTOA. Pericytes will be visualized and/or isolated by their fluorescent reporter activity. Pericyte numbers, distribution, and immunomodulatory function will be correlated with the degree of joint space inflammation and the severity of joint damage. Aim 2: Evaluate the therapeutic potential of intra-articular pericyte delivery in mouse PTOA. Next, the use of pericytes as a non-invasive cell therapy for PTOA will be assessed. Mouse pericytes will be isolated and applied by joint space injection to mice after establishing PTOA. Injection without cells will be used as a control. The severity of PTOA will be assessed with or without pericyte treatment. In summary, the current proposal is a high-risk/high-reward line of investigation that proposes to lay the groundwork for future studies in harnessing the power of pericyte immunomodulation in joint pathologies. If successful, this Discovery Award could pave the way for a new, safe, and efficacious cellular therapy for osteoarthritis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810121
Entities
People
- Aaron W James
Organizations
- Johns Hopkins University
- United States Army