New therapeutic approaches for protecting hematopoietic stem cells in aplastic anemia

Abstract

Aplastic anemia (AA) is an immune-mediated and life-threatening form of acquired bone marrow failure (BMF), characterized by development and expansion of self-reactive T cells. These T cells cause continuous destruction of hematopoietic stem cells (HSCs), progenitors, and mature blood cells, leading to severe and if left untreated fatal marrow hypoplasia and pancytopenia. Standard treatment options for patients with AA include: (1) immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine A which targets self-reactive T cells, or (2) matched sibling or unrelated BM transplant (BMT). The IST treatment is often not effective due to poor response to therapy or disease relapse after IST. Also, BMT is not an option for many patients due to their age, comorbidities, and the lack of histocompatible donor. This necessitates development and testing of novel approaches to reduce severity of AA and to efficiently treat patients with refractory and relapsed AA. Immune-mediated AA was reproduced in animals, including mouse lymphocyte infusion models, which are used to study further etiology and pathophysiology of AA and test new drugs and approaches in treating and managing AA. In these mouse models the immune correlates and pathologic features of AA are strikingly similar to features of severe human AA. In this article we (a) briefly review standard and developing approaches for treating AA and (b) describe development and testing of novel treatment approach with a potential to safely reduce BM hypoplasia and significantly decrease the loss of HSCs in mouse lymphocyte infusion model of AA.

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

“…The disorder of immune system especially T cells plays an important role in the development of AA. Therefore, immune reconstitution is very important in the treatment of AA (Weston et al, 2013). Our results showed that the oral administration of TSDN preparation caused a significant increase in the percentages of CD3 þ , T-helper cells (CD4 þ Th cells) and a decrease in the percentage of T-cytotoxic/ suppressor cells (CD8 þ Tc cells) in AA mice BMNC, respectively.…”

Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of literature

“…Its causes are various, and it is regarded as an autoimmune disorder55 in which immune cells (mainly T cells)56 attack the bone marrow and cause pancytopenia. Its first-line treatment consists of hematopoietic cell transplantation and administration of immunosuppressive drugs.…”

New insights on stem cells modeling and treatment of human diseases

“…Yet, IST approach is often not applicable due to poor response or relapse post IST. As with leukemia, bone marrow transplants are not an ideal option due to lack of histocompatible donor, age, comorbidities, etc (30)(31)(32). Maiguel et al (2011) have discovered a drug named leukadherins, which protects HSCs from self-reactive effector T cell in AA condition, thus reducing the loss of HSCs and its progenitor cells in immune-mediated AA, improving Figure 1.…”