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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1259-1261.
Prepublished online as a Blood First Edition Paper on May 5, 2005; DOI 10.1182/blood-2005-03-1081.


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HEMATOPOIESIS
Brief report

Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells

Joby L. McKenzie, Olga I. Gan, Monica Doedens, and John E. Dick

From the Department of Molecular and Medical Genetics, University of Toronto and Division of Cell and Molecular Biology, University Health Network, Toronto, ON, Canada.

The nonobese diabetic/severe combined immune deficiency (NOD/SCID) xenotransplantation model has emerged as a widely used assay for human hematopoietic stem cells; however, barriers still exist that limit engraftment. We previously identified a short-term SCID-repopulating cell (SRC) following direct intrafemoral injection into NOD/SCID mice, whereas others characterized similar SRCs using NOD/SCID mice depleted of natural killer (NK) cell activity. To determine the model that most efficiently detects short-term SRCs, we compared human engraftment in 6 different xenotransplantation models: NOD/SCID-{beta}2-microglobulin-null mice, anti-CD122 (interleukin-2 receptor {beta} [IL-2R{beta}])–treated or unmanipulated NOD/SCID mice, each given transplants by intravenous or intrafemoral injection. Human cell engraftment was highest in intrafemorally injected anti-CD122–treated NOD/SCID mice compared to all other groups at 2 and 6 weeks after transplantation. These modifications to the SRC assay provide improved detection of human stem cells and demonstrate that CD122+ cells provide barriers to stem cell engraftment, a finding with potential clinical relevance.


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