ADVANCES IN HEMATOPOIETIC STEM-CELL CULTURE

Recent advances in our understanding of the earliest stages of hematop oietic cell differentiation, and how these may be manipulated under de fined conditions in vitro, have set the stage for the development of r obust bioprocess technology applicable to hematopoietic cells. Sensiti ve and specific assays now exist for measuring the frequency of hemato poietic stem cells with long-term in vivo repopulating activity from h uman as well as murine sources. The production of natural or engineere d ligands through recombinant DNA and/or combinatorial chemistry strat egies is providing new reagents for enhancing the productivity of hema topoietic cell cultures. Multifactorial and dose-response analyses hav e yielded new insight into the different types and concentrations of f actors required to optimize the rate and the extent of amplification o f specific subpopulations of primitive hematopoietic cells. In additio n, the rate of cytokine depletion from the medium has also been found to be dependent on the types of cell present. The discovery of these c ell-type-specific parameters affecting cytokine concentrations and res ponses has introduced a new level of complexity into the design of opt imized hematopoietic bioprocess systems.