Ex vivo expansion of hematopoietic cells: What is the clinical need?

Although hematopoietic transplantation has been performed for 40 years or more, we still cannot fully define what constitutes an optimal cell graft. We do not have clear phenotypical or functional definitions of the cell or cells that provide early engraftment of neutrophils or platelets. Although stem cells can be assayed in mouse models, there is no assay for hematopoietic stem cells that has been demonstrated to correlate with long-term engraftment in patients. In fact, we do not even know what the life span of a hematopoietic stem cells is! Do human hematopoietic stem cells have a similar life span as mouse stem cells (3-5 years) or do they persist for the duration of an individual's life, possibly 70 years or longer? How do we design studies to demonstrate a correlation of the surrogate hematopoietic stem cells assays with long-term outcome in patients? There clearly are a host of outstanding questions that will require many years of careful research before we even begin to understand the role of the different cell populations that make up hematopoietic cells grafts. The major clinical need for expansion at this time is in the use of cord blood (CB) products, which are associated with significant periods of neutropenia and thrombocytopenia and short-term engraftment failure. We believe this can be improved with increased numbers of mature cells and committed progenitor cells that can be provided with ex vivo expansion of a fraction of the CB product.