Stem cell assays in the evaluation of myelotoxicity

The concept and characteristics of different types of hematopoietic cells have been described. Hematopoietic stem cells are currently considered to exist in a variety of populations with different degrees of commitment towards a particular cell line. By a combination of animal studies and studies with hematopoietic disorders, the concept of dividing hematopoietic stem cells into uncommitted and committed types has emerged in the past several years. Uncommitted stem cells are capable of differentiation, under the proper stimulus, into either of the cell lines of the hematopoietic system. These cells form a resting population of cells with a low mitoitic rate and a long resting (G(0)) phase. The committed stem cells are partially differentiated and mature only into one type of cell. The committed stem cell population is relatively more active than the population of uncommitted stem cells. A variety of assays both in vivo and in vitro are currently available for the study of different hematopoietic stem cells. These assays are semiquantitative. The number of colonies of mature cells which develop after the infusion or plating of a population of cells containing the stem cells is proportional to the total number of cells infused. A variety of toxic as well as biological substances have been assayed in these systems and a quantitative depression of the number of colonies produced has been noted by a variety of workers. The degree of depression in the number of colonies varies with the agent in use and the type of assay employed. These studies have demonstrated that toxicity of chemicals on the hematopoietic stem cells can be studied with these in vitro and animal studies to give an assessment of their potential toxicity in the intact organism. The recent development of the Dexter two-layer liquid culture system has provided a new impetus to the research on the uncommitted stem cell in a variety of organisms.