A novel etiology of aplastic anemia: the uncontrolled adipogenic differentiation of mesenchymal stem cells in bone marrow induced by an abnormal immunological reaction

Aplastic anemia (AA) is a clinical syndrome manifested by cytopenia and the fatty replacement of the marrow with a near absence of hematopoietic precursor cells. The present review explored the pathological roles of adipocytes in AA. The original articles and critical reviews selected were relevant to aplastic anemia, mesenchymal stem cells and adipocytes. The following well-documented evidence demonstrates that over adipogenesis has negative effects on aplastic anemia. 1) Increasing evidence indicates that toxins and toxic drugs that can frequently lead to AA can concomitantly induce mesenchymal stem cells (MSCs) to undergo adipogenesis. 2) The response time of immunosuppressive therapy for AA is significantly longer than that of other immuno-related cytopenia disorders, such as immune thrombocytopenia, indicating that not only hematopoietic cells but also possibly MSCs are targeted by abnormal immune status in AA patients. 3) Both the immunosuppressive and androgen therapies used for AA can decrease the adipogenesis of MSCs in the marrow. 4) A number of myelosuppressive cytokines, including tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon (IFN-γ), can be produced by adipose tissue. Exorbitant adipogenesis can directly inhibit hematopoiesis in animal models. This novel etiological model is worthy of further corroboration via experiments. If this finding is valid, the therapeutic modality would undoubtedly shift from immune suppression to the combination of immune suppression and the interference of the pathway involved in the adipogenesis of MSCs. The findings suggest the uncontrolled adipogenic differentiation of mesenchymal stem cells in bone marrow induced by an abnormal immunological reaction, which is a novel etiology of aplastic anemia. DOI: 10.11855/j.issn.0577-7402.2014.03.01