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

• Published in: Blood Vol. 106; no. 4; pp. 1259 - 1261
• Main Authors: McKenzie, Joby L., Gan, Olga I., Doedens, Monica, Dick, John E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2005
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacology; beta 2-Microglobulin - deficiency; Femur; Hematopoiesis; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - standards; Hematopoietic Stem Cells - cytology; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Models, Animal; Receptors, Interleukin-2 - deficiency; Receptors, Interleukin-2 - immunology; Receptors, Interleukin-2 - physiology; Transplantation, Heterologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-03-1081

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-β2-microglobulin-null mice, anti-CD122 (interleukin-2 receptor β [IL-2Rβ])–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.