HUMAN PERIPHERAL-BLOOD STEM-CELLS

''Peripheral blood stem cells'' (PBSC) usually refer to apheresis products collected in patients primed with chemotherapy and/or recombinant hematopoietic growth factors such as granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage-colony stimulating factor (GM-CSF). The proportion of true ''stem cells'' in these cell populations is very small, much smaller than the frequency of other, more mature progenitors, or of differentiated cells. However, the use of apheresis products has greatly changed the clinical practice of high-dose chemotherapy over the last few years. Harvesting is easy and does not require general anesthesia, as does bone marrow collection. Time to hematopoietic recovery is usually shorter in patients receiving PBSC as compared to patients receiving bone marrow. In association with the use of hematopoietic growth factors during chemotherapy-induced cytopenia, PBSC help reduce morbidity associated with high-dose chemotherapy, and thus allow more patients with poor risk cancer to benefit from this technique. Many scientific questions remain unsolved. Identification of stem cells is still hampered by the lack of a simple and reproducible in vitro assay. These difficulties do not allow to accurately appreciate the contribution of different populations of progenitors to hematopoietic recovery, and thus to predict the quality of a hematopoietic graft. The ability of PBSC to repopulate lymphoid lineages is poorly defined. Despite these uncertainties, PBSC have numerous potentialities. Associated with the clinical use of techniques such as selection of normal progenitors (based on the expression of the CD34 antigen for example), or liquid cultures supplemented with recombinant cytokines (the so-called ''ex-vivo expansion''), they offer the opportunity to change the balance between normal hematopoietic progenitors on one hand, and residual tumor cells or accessory cells such as T lymphocytes on the other hand. As a consequence, purging or prevention of graft-versus-host disease with T cell depletion can be envisioned from a new standpoint. Finally, PBSC represent a very interesting target for genetic manipulations. These multiple potentialities explain why the use of apheresis products contributes to broaden the application of hematopoietic stem cell transplantation, a practice that in many cases comes closer to transfusion. It also explains why PBSC already appear as a matter of economic and ethical controversies, being one of the first widely used ''cellular therapies''.