Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells.
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-beta2-microglobulin-null mice, anti-CD122 (interleukin-2 receptor beta [IL-2Rbeta])-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.
McKenzie
Joby L
JL
Department of Molecular and Medical Genetics, University of Toronto, ON, Canada.
Gan
Olga I
OI
Doedens
Monica
M
Dick
John E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D005269:Femur; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000276:immunology / Q000502:physiology; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000172:deficiency
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D001613:beta 2-Microglobulin