Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin 
chain of the adult hemoglobin gene. This results in excess accumulation of 
unpaired alpha-chain gene products leading to reduced red blood cell life span 
and the development of severe anemia. Current treatment of this disease involves 
regular blood transfusion and adjunct chelation therapy to lower blood 
transfusion-induced iron overload. Fetal hemoglobin switching agents have been 
proposed to treat genetic blood disorders, such as sickle cell anemia and 
beta-thalassemia, in an effort to compensate for the dysfunctional form of the 
beta-globin chain in adult hemoglobin. The rationale behind this approach is to 
pair the excess normal alpha-globin chain with the alternative fetal gamma-chain 
to promote red blood cell survival and ameliorate the anemia. Reprogramming of 
differentiation in intact, mature, adult white blood cells in response to 
inclusion of monoclonal antibody CR3/43 has been described. This form of 
retrograde development has been termed "retrodifferentiation", with the ability 
to re-express a variety of stem cell markers in a heterogeneous population of 
white blood cells. This form of reprogramming, or reontogeny, to a more 
pluripotent stem cell state ought to recapitulate early hematopoiesis and 
facilitate expression of a fetal and/or adult program of hemoglobin synthesis or 
regeneration on infusion and subsequent redifferentiation. Herein, the outcome 
of infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients 
with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous 
RSC subjected to hematopoietic-conducive conditions into patients with 
beta-thalassemia reduced mean blood transfusion requirement, increased mean 
fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This 
was always accompanied by an increase in mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration 
(MCHC) in such patients. No adverse side effects in response to the infusion of 
autologous RSC were noted. This novel clinical procedure may profoundly modify 
the devastating course of many genetic disorders in an autologous setting, thus 
paving the way to harnessing pluripotency from differentiated cells to 
regenerate transiently an otherwise genetically degenerate tissue such as 
thalassemic blood.