Allogeneic stem cell transplant is the only curative therapy for many high risk blood cancers however, its success can be limited by graft-versus-host disease (GVHD), an inflammatory, immune-mediated disorder which can cause damage to organs. Despite prevention, GVHD may occur in up to half of patients undergoing a transplant, and only half of these patients respond to first-line therapy with steroids. These “steroid-refractory” patients are predominantly affected by gastrointestinal GVHD.
Mesenchymal stem cells (MSCs) are cells which have immunomodulatory, anti-inflammatory, and tissue regenerative properties and have been studied in steroid-refractory acute GVHD with varying effects. Although studies have demonstrated safety and the potential to treat acute GVHD with MSCs, further research is needed to determine optimal formulation and delivery for efficacy. Bone marrow derived (bm) exosomes, nanovesicles secreted by MSCs, are a novel product with therapeutically active components and functions (anti-infammatory, regenerative, immunomodulatory) of MSCs. They provide a number of advantages including a superior safety profile, stability and scalability. Several studies have demonstrated the favorable therapeutic effects of MSC exosomes in a variety of inflammatory diseases, including GVHD mouse models.
We thus propose to investigate the benefits of bmMSC exosomes in transplant recipients with gastrointestinal GVHD. We aim to evaluate the safety and efficacy of intravenous as well as direct injection of bmMSC exosomes for the treatment of high risk and steroid-refractory gastrointestinal GVHD. We also aim to further understand the mechanisms of bmMSC exosomes on GVHD using laboratory intestinal models.
This project aims to find better treatment approaches to graft-versus-host disease, making the curative therapy of bone marrow transplant safer for patients with blood cancers.