ENGRAFTMENT AND DEVELOPMENT OF HUMAN CD34(-ENRICHED CELLS FROM UMBILICAL-CORD BLOOD IN NOD())LTSZ-SCID/SCID MICE/

Understanding the repopulating characteristics of human hematopoietic stem/progenitor cell fractions is crucial for predicting their perform ance after transplant into high-risk patients following high-dose ther apy. We report that human umbilical cord blood cells, 78% to 100% of w hich express the hematopoietic progenitor cell surface marker CD34, ca n consistently engraft, develop, and proliferate in the hematopoietic tissues of sublethally irradiated NOD/LtSz-scid/scid mice. Engraftment and development of CD34(+) cells is not dependent on human growth fac tor support. CD34(+) cells home to the mouse bone marrow (BM) that bec omes the primary site of human hematopoietic development containing my eloid, lymphoid, erythroid, and CD34(+) progenitor populations. Myeloi d, and in particular lymphoid cells possessing more mature cell surfac e markers, comprise the human component of mouse spleen and peripheral blood, indicating that development proceeds from primary hematopoieti c sites to the periphery. Repopulation of secondary recipients with hu man cells by BM from primary recipients demonstrates the maintenance o f substantial proliferation capacity of the input precursor population . These data suggest that the cells capable of initiating human cell e ngraftment (SCID-repopulating cells) are contained in the CD34(+) cell fraction, and that this mouse model will be useful for assaying the d evelopmental potential of other rare human hematopoietic cell fraction s in vivo. (C) 1997 by The American Society of Hematology.