Mesenchymal Stem Cells as a Treatment for Oral Complications of Graft-versus-host Disease

Graft -Versus-host-disease

Graft-versus-host-disease, Immune system diseases, Oral

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), and is classified as acute (aGVHD) or chronic (cGVHD). aGVHD onsets within the first 100 days after transplant or with clinical features including erythema, liver dysfunction and oral mucositis, whilst cGVHD or persistent GVHD occurs in approximately 30-60% of transplant patients who survive their first year . Long-term five-year prognosis for cGVHD patients is poor with a 70% mortality rate. cGVHD manifests as an autoimmune-like disease affecting multiple sites, including skin, mouth, eyes, gastrointestinal tract, liver, and joints. The oral cavity is the second most common site to be affected with symptoms in 45-83% of cases. In the mouth a diverse spectrum of clinical features can be found for example mucosal lesions can affect almost any site, salivary gland dysfunction and restricted mouth opening. Short-term patients can experience mucosal sensitivity, malnutrition, problems speaking, increased caries risk, xerostomia, oral pain and a diminished quality-of-life. Long-term complications include secondary malignancies and perhaps early death. Clinical management seeks to alleviate the symptoms and improve quality-of-life but 50% of patients fail front-line systemic steroid therapy. Oral cGVHD can be treated with topical high potency corticosteroids and oral rinses, however these treatments are not always effective and carry a risk of systemic absorption. Mesenchymal stem/stromal cells (MSCs) resident in adult and fetal tissues, such as the bone marrow have the capacity to form bone, cartilage, stroma, muscle and fat, are known to exhibit immunosuppressive and immunoregulatory properties both in vivo and in vitro. MSC infusions have been used to treat disorders such as osteogenic imperfecta, cardiovascular disease and to heal large bony defects. Indeed, the immunosuppressive capacity of MSCs have led to infusions being used as a second-line treatment for GVHD patients, and our group has shown within a Phase II clinical trial, 55% aGVHD patients who failed front-line steroid treatment responded to MSC infusion these studies are going with cGVHD patients. The goal of this project is to perform a pilot study to determine whether MSC injections directly into mucosal lesions in patients with oral cGVHD are able to alleviate the symptoms and facilitate the reparative process.

No related papers found yet.

Sweden