Background and objectives: The disease, aplastic anaemia is a life threatening rare bone marrow failure. In this condition the underlying haematopoietic cellular deficit, lead to hemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia; extending this benefit to older patients or those lacking a family donor remains a major challenge. Herein, the safety and efficacy of infusing autologous haematopoietic retrodifferentiated stem cells into four patients with aplastic anaemia without the use of any pre or post-conditioning regimen including immunosuppression is described. Methods: Un-mobilized, mononuclear cells were harvested from 4 patients with acquired aplastic anaemia by aphaeresis. Mononuclear cells of patients were cultured with purified monoclonal antibody against the monomorphic regions of the beta chain of MHC class II antigens (Clone CR3/43) for 3 hours, to obtain autologous retrodifferentiated haematopoietic stem cells (RHSC). Autologous RHSC were washed and infused into the 4 patients without the use of any pre or post-conditioning regimen. Thereafter, the efficacy (engraftment) of autologous RHSC was assessed in these four patients. Results: Following single infusion of the autologous RHSC, 2 out of 4 patients with aplastic anaemia are now transfusion independent for more than 6 years. This mode of engraftment is similar to those obtained following transfusion of stem cells from identical twins in the absence of any pre-conditioning regimen. Most importantly, karyotyping and G-banding analysis prior and post procedure in all patients remained the same, indicating that the retrodifferentiated stem cells possess long term repopulation potentials and are safe. Interpretation and conclusion: This is the first report demonstrating the functional utility of reprogrammed fully differentiated adult cells into pluripotent stem cells with extensive repopulation potentials in a human setting and without any pre or post conditioning regimen, including immunosuppression. This autologous approach of stem cell creation may broaden the curative potentials of stem cell therapy to a wider population of patients with aplastic anaemia, including many patients suffering from other haematological and non-haematological disorders. Key Words: Retrodifferentiation, Aplastic Anemia, Autologous Stem Cells, reprogrammed Mature Adult Cells, Leukocytes, Induced Pluripotent Stem Cells.
Autologous Stem Cells
Reprogrammed Mature Adult Cells