Improvement of hematopoietic stem cell transplantations by ex vivo manipulation of donor stem and progenitor cells

Many hematologic disorders can only be cured by hematopoietic stem cell transplantation (HSCT). Clinical experience has shown that higher donor stem cell (HSC) counts are able to accelerate engraftment while lowering transplantation-associated risks. Therefore, much effort is put into strategies to enhance HSC numbers (i.e. expansion). We have previously shown that a relevant number of HSCs dies during engraftment and that the pro-apoptotic Bcl-2 proteins Bim and Bmf are central players. Inhibition of either protein was sufficient to increase stem cell survival and transplantation efficacy. However, since perman…