Significance of the SCID mouse models for the study of normal and leukemic human hemopoiesis and gene therapy

The hemopoietic system is organized as a hierarchy with all myeloid and 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 been 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 transplantation system can be used to characterize and purify candidate human stem cell populations. Moreover, recent studies have provided strong support for the concept that there is a hierarchy of stem and progenitor 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 transfer into primitive genetically deficient stem cells following engraftment in immune-deficient mice. Potentials and limitations of the different approaches are discussed.