SIGNIFICANCE OF THE SCID MOUSE MODELS FOR THE STUDY OF NORMAL AND LEUKEMIC HUMAN HEMATOPOIESIS AND GENE-THERAPY

The hemopoietic system is organized as a hierarchy with all myeloid an d lymphoid cells arising from a small number of pluripotent stem cells . As current in vitro methods do not assay stem cells, transplantation -based models for normal and leukemic human hemopoietic cells have bee n developed using immune-deficient mice as recipients. In vivo models were established for adult, neonatal, and fetal human hemopoiesis, for human leukemias and for genetic disorders and gene therapy. This tran splantation system can be used to characterize and purify candidate hu man stem cell populations. Moreover, recent studies have provided stro ng support for the concept that there is a hierarchy of stem and proge nitor cells for human leukemias. The SCID mouse models enable analysis of the biology of and metabolization of cytostatic drugs by leukemic stem cells. In addition, they are an important tool in developing and improving gene therapy protocols by assessing the efficiency of gene t ransfer into primitive genetically deficient stem cells following engr aftment in immune-deficient mice. Potentials and limitations of the di fferent approaches are discussed.