Identification of compounds protecting donor stem cells from apoptosis and increasing efficacy of hematopoietic stem cell transplantation

HSCT is the only curative treatment for many hematological and immunological diseases but is hampered by the risk of graft failure or delayed engraftment. In previous studies we have identified two Bcl-2 proteins from the pro-apoptotic BH3-only subgroup, Bim and Bmf, to be central players in apoptosis induction of hematopoietic stem and progenitor cells (HSPCs) during transplantation. Permanent inhibition of either protein was sufficient to significantly increase donor cell performance, but at the same time triggered malignant transformation and autoimmunity. We here aim to inhibit apoptosis transiently for ther…