Mesenchymal stromal cells: filling the void of immunosuppressive therapy in aplastic anemia?

Abstract

Mesenchymal stromal cells (MSCs) have been used in the context of hematopoietic stem cell transplantation (HSCT) to treat graft-versus-host disease and stimulate tissue repair. Their relative ease of manufacture, immunomodulatory, differentiation and regenerative properties, weak recognition by host immunity, and favorable risk profile make MSCs attractive in inducing tolerance in the setting of transplantation and autoimmunity (1). Recently, coculture of MSCs with umbilical cord blood cells have led to rapid engraftment comparable to that of an adult donor graft (2). MSC treatments have also been applied in autoimmune disease such as inflammatory bowel disease and multiple sclerosis and in tissue repair in degenerative conditions such as amyotrophic lateral sclerosis (3). In the next few years we can expect the role of MSC in HSCT and autoimmune diseases to be increasingly defined in this rapidly evolving field. Aplastic anemia (AA) is characterized by pancytopenia and a marked reduction in stem and progenitor marrow cells. Evidence from the laboratory, animal models and from the clinic strongly support and autoimmune pathogenesis where effector T cells recognize and destroy marrow elements, resulting in a hypocellular bone marrow (5). More recently, decreased regulatory T (Tregs) and increased TH17 cells have been described in AA patients at presentation, with improvement of this ratio after successful immunosuppressive therapy (4). Anti-thymocyte globulin (ATG) is the primary immunosuppressive agent used in severe AA inducing hematological responses in 60-75% of patients when combined with cyclosporine (5). The mechanism(s) by which ATG restores hematopoiesis in aplastic