Potentials and possible pitfalls of human stem cell analysis.

A clonogenic cell assay for malignant brain tumors that permits the evaluation of tumor cell sensitivity to BCNU and that correlates with patient response to BCNU has been developed. The potential for a stem cell analysis of human tumors has been demonstrated by studies of the reasons for clinical drug failure, tumor heterogeneity, and age-response relationships. The basic requirements of a stem cell assay include the ability to dissociate representative single cells from solid tumors, to optimize culture conditions, and to characterize the growth of colonies. Exposure of cells to a drug in vitro must be comparable to the in situ situation; possible significant differences between short-term and "continuous" treatment methods are emphasized. Also discussed are criteria for in vitro sensitivity of cells, problems inherent in the "early" evaluation of cultures (at the cell "cluster" stage), and the effects of system errors, which if overcome should lead to the development of analytic methods with a maximum sensitivity and predictive value.