STEM-CELLS - CHARACTERIZATION AND MEASUREMENT

The process of blood formation is sustained throughout an individual's life by a small population of haemopoietic stem cells (HSCs). The HSC compartment represents a hierarchy of HSC subsets with decreasing pro liferative ability. This heterogeneity is reflected in the varying tim e periods that HSCs may contribute to the initiation and maintenance o f donor-type haemopoietic multilineage chimerism in vivo. The phenotyp e of HSC is incompletely defined rendering morphological or flow cytom etric quantitation unreliable. Functional HSC assays, both in vitro (C AFC, LTC-IC) and in vivo (repopulation of NOD/SCID mice) may be superi or to phenotypic analysis; however, such assays have not been truly va lidated in a human transplant setting. The quiescence and proliferatio n of HSCs is highly regulated by the stroma in haemopoietic organs. Ma ny of the cytokines that have been cloned in recent years are actually elaborated and presented by the haemopoietic organ stroma and are sup posed to serve as local regulators in order to gain specificity and av oid pleitropic and thus undesired side effects. Most probably, additio nal stroma-derived factors will be characterized as suggested by the o bservation that HSCs produce more progeny in stroma-contact than in it s absence or in stroma-conditioned medium, irrespectively of the exoge nous cytokines included. Stem cells are considered to possess the abil ity to self-renew and are therefore attractive vehicles for gene thera py. The same assumed characteristic fuels attempts to amplify their nu mbers ex vivo, and is expected to enable more rapid haemopoietic recov ery of conditioned recipients as well as enlarge HSC grafts of insuffi cient size before actual transplantation.