Establishment of Assays for Human Hematopoietic Cells in Immune Deficient Mice

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Abstract
Understanding the process of differentiation and development remains as a major challenge in biology. The hematopoietic system offers unique advantages for such studies. The blood-forming system of mice and humans consists of a heterogeneous array of cells, ranging from large numbers of differentiated cells with defined function to rare pluripotent stem cells with considerable developmental and proliferative potential (Till and McCulloch 1980). The reason this complex developmental system has proved to be so malleable for experimentation rests in the availability of quantitative colony assays for committed and multilineage progenitor cell types. Although no colony assays exist for the earliest cells in the murine stem cell hierarchy, they can nevertheless be indirectly assayed by reconstitution of lethally irradiated or genetically deficient mice. A large body of knowledge has accumulated over the past 25 years about the various classes of progenitor and stem cells, as well as the factors and cell-cell interactions that regulate their developmental program. Although in vitro colony assays exist for committed and multilineage human progenitor cells, our understanding of the biology of the human hematopoietic system has suffered relative to that in the mouse because of the lack of an in vivo assay system for human pluripotent stem cells. Several groups have recently reported the engraftment of immunedeficient mice with human lymphoid (Mosier et al 1988; McCune et al 1988) and myeloid hematopoietic cells (Kamel-Reid and Dick 1988). These animals offer an enormous opportunity to examine the human hematopoietic system and may lay the foundation for a human stem cell assay. This paper will briefly review our efforts to establish normal human hematopoietic cells in immunedeficient animals and examine the potential application of this approach to study human leukemic transformation.