HEMATOPOIETIC STEM-CELLS - ANALYSIS OF SOME PARAMETERS CRITICAL FOR ENGRAFTMENT

In this review four parameters relevant to the grafting of hemopoietic stem cells (HSC) are analyzed: the nature and amounts of grafted HSC, the sources of HSC and the ''in vivo'' fate of the grafted cells. One may oppose cells with short-term repopulating ability to cells with l ong-term reconstitutive capacity. The former comprise progenitors, whi le the latter consist of primitive stem cells, corresponding to murine pre-colony forming units-spleen (pre-CFU-S) (and to some murine CFU-S ) or to human pre-colony forming units (pre-CFU). In the mouse, the nu mber of progenitors involved in short-term reconstitution is large, wh ile that of primitive cells operating months after the transplantation is reduced. These results may be extrapolated to humans, suggesting t hat it is possible to engraft a limited number of genetically modified HSC. However, the administration of large numbers of reconstituting c ells appears to be a cautionary procedure, since it should insure poly clonal hemopoiesis, which is the physiological situation in mammals. B esides marrow, peripheral blood from adult patients treated with chemo therapy and growth factors, and cord blood from newborns, are promisin g sources of HSC. Successful engraftment depends not only on the quali ty and quantity of HSC, but also on the integrity of the marrow microe nvironment. This microenviromnent may be impaired by chemo- and radiot herapy, which provides a theoretical basis for the transplantation of stromal cells along with that of HSC.