RETENTION AND MULTILINEAGE EXPRESSION OF HUMAN HEMATOPOIETIC STEM-CELLS IN HUMAN SHEEP CHIMERAS

We have taken advantage of the permissive environment of the preimmune fetus to achieve engraftment of hematopoietic stem cells (HSC) from f etal and postnatal human sources in sheep, The resulting chimeric lamb s exhibited long-term multilineage (erythroid, myeloid, lymphoid) expr ession of donor cells that remained responsive to human-specific cytok ines, The small size of the fetus allowed the assessment of the engraf tment potential of relatively small numbers of highly characterized hu man HSC populations, while the large size of the chimeric sheep permit ted the long-term evaluation of the HSC activity and response in vivo. The human/sheep xenograft may offer a useful large animal model for t he assay and long-term study of the human HSC subsets,