Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients.
Repopulation of immunodeficient mice remains the primary method to assay human hematopoietic stem cells (HSCs). Here we report that female NOD/SCID/IL-2Rg(c)-null mice are far superior in detecting human HSCs (Lin(-)CD34(+)CD38(-)CD90(+)CD45RA(-)) compared with male recipients. When multiple HSCs were transplanted, female recipients displayed a trend (1.4-fold) toward higher levels of human chimerism (female vs male: injected femur, 44.4 +/- 9.3 vs 32.2 +/- 6.2; n = 12 females, n = 24 males; P = .1). Strikingly, this effect was dramatically amplified at limiting cell doses where female recipients had an approximately 11-fold higher chimerism from single HSCs (female vs male: injected femur, 8.1 +/- 2.7 vs 0.7 +/- 0.7; n = 28 females, n = 20 males; P < .001). Secondary transplantations from primary recipients indicate that females more efficiently support the self-renewal of human HSCs. Therefore, sex-associated factors play a pivotal role in the survival, proliferation, and self-renewal of human HSCs in the xenograft model, and recipient sex must be carefully monitored in the future design of experiments requiring human HSC assays.
Notta
Faiyaz
F
Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, ON, Canada.
Doulatov
Sergei
S
Dick
John E
JE
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D049109:Cell Proliferation; D046528:Chimerism; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D015375:Receptors, Interleukin-2