A CELLULAR-MODEL FOR DRUG-INTERACTIONS ON HEMATOPOIESIS - THE USE OF HUMAN UMBILICAL-CORD BLOOD PROGENITORS AS A MODEL FOR THE STUDY OF DRUG-RELATED MYELOSUPPRESSION OF NORMAL HEMATOPOIESIS

A cellular model of hematopoiesis which would be more convenient than bone marrow (BM) progenitors and directly relevant to human pathology is needed in order to investigate xenobiotic toxicity. Human umbilical cord blood (HCB), previously shown to be able to repopulate BM, provi des a powerful in vitro model of normal human hematopoiesis. In order to validate the use of normal HCB progenitors as targets for dose-rela ted myelosuppression, we used clonogenic assays and expansion in a liq uid culture of progenitor-enriched cell suspensions from HCB. A series of 8 reference molecules, doxorubicin, cytosine-arabinoside, 5-fluoro uracil, 3'-azido-3'-deoxythymidine, acetylsalicylic acid, sodium valpr oate and two cephalosporin antibiotics, were tested. In vitro 50% inhi bition concentrations (IC50) were compared to those observed or report ed with BM progenitors, and to the values of plasma concentrations fro m treated patients. HCB progenitors as in vitro targets for cytotoxic molecules were easy to access and handle, and their use was sensitive, specific and reproducible. They gave results similar to BM progenitor s and allowed a qualitative approach to cellular metabolism and toxici ty using morphological, flow cytometric and chromatographic methods.