Controlling culture dynamics for the expansion of hematopoietic stem cells

The ex vivo expansion of hematopoietic stem cells (HSCs) is the subject of intense commercial and academic interest due to the potential of HSCs to be a renewable source of material for cellular therapeutics. Unfortunately, b ecause methodologies have not yet been developed to grow clinically relevan t numbers of HSCs (or their derivatives) consistently, the potential of thi s technology is limited. Manipulation of the in vitro culture microenvironm ent, primarily through cytokine supplementation, has been the predominant a pproach in studies attempting to expand primary human HSC numbers in vitro. While promising results have been obtained, it is becoming clear that nove l methods must be developed before cellular therapies using these stem cell s can become routine. Ideally, bioprocesses must be designed to target spec ifically the growth of stem cell populations while incorporating positive a nd negative feedback from potentially dynamic mature and maturing cell popu lations. The product of these culture systems should consist of not only HS Cs, but also of cells that allow the engraftment of HSCs and, ideally, cell s responsible for the immediate or accelerated functional support of patien ts. Development of such "designer transplants" will require combining optim al culture conditions capable of amplifying HSC numbers with novel approach es for finely controlling the number, functional capabilities, and characte ristics of potentially therapeutic cells in these very complex cell culture systems.