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Engraftment and Development of Human CD34+-Enriched Cells From Umbilical Cord Blood in NOD/LtSz-scid/scid Mice

Christopher J. Hogan, Elizabeth J. Shpall, Oren McNulty, Ian McNiece, John E. Dick, Leonard D. Shultz, and Gordon Keller

From the Bone Marrow Transplant Program, the Division of Medical Oncology, and the Department of Immunology, University of Colorado Health Sciences Center, Denver; National Jewish Center for Immunology and Respiratory Medicine, Denver, CO; Amgen, Thousand Oaks, CA; the Department of Molecular and Medical Genetics, University of Toronto and the Department of Genetics, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and The Jackson Laboratory, Bar Harbor, ME.

Understanding the repopulating characteristics of human hematopoietic stem/progenitor cell fractions is crucial for predicting their performance after transplant into high-risk patients following high-dose therapy. We report that human umbilical cord blood cells, 78% to 100% of which express the hematopoietic progenitor cell surface marker CD34, can 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 factor support. CD34+ cells home to the mouse bone marrow (BM) that becomes the primary site of human hematopoietic development containing myeloid, lymphoid, erythroid, and CD34+ progenitor populations. Myeloid, and in particular lymphoid cells possessing more mature cell surface markers, comprise the human component of mouse spleen and peripheral blood, indicating that development proceeds from primary hematopoietic sites to the periphery. Repopulation of secondary recipients with human cells by BM from primary recipients demonstrates the maintenance of substantial proliferation capacity of the input precursor population. These data suggest that the cells capable of initiating human cell engraftment (SCID-repopulating cells) are contained in the CD34+ cell fraction, and that this mouse model will be useful for assaying the developmental potential of other rare human hematopoietic cell fractions in vivo.

Blood, Vol. 90 No. 1 (July 1), 1997: pp. 85-96
© 1997 by The American Society of Hematology.


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