Cytokine combinations for the in-vivo and ex-vivo expansion of hematopoietic progenitor cells

The critical role of hematopoietic progenitor cells (HPC) for the formation of mature blood cells is well established. Interleukin-3 (IL-3), stem cell factor (SCF), and flt3-ligand (FL) are potential candidates for expansion strategies due to their early acting and lineage-unspecific hematopoietic stimulation. In preclinical and clinical models IL-3, SCF, and FL induced in-vivo expansion of the progenitor cell pool has been shown to be associated with increased KPC-mobilization by G-CSF, reduction in the number of leukaphereses required to obtain adequate HPC-numbers and the potentiation of lineage-specific growth factors. Early acting cytokines are also crucial for ex-vivo expansion strategies and are here important partner molecules for IL-1, IL-6 and IL-10. In-vivo as well as ex-vivo expanded HPC are able to reconstitute hematopoiesis in patients following myeloablative chemoradiotherapy. Thus expanded HPC will be increasingly used for clinical purposes and facilitate therapeutic strategies which are currently limited by the problem of insufficient HPC-numbers.