Variables to predict engraftment of umbilical cord blood into immunodeficient mice: usefulness of the non-obese diabetic--severe combined immunodeficient assay.
Umbilical cord blood is an alternative stem cell source for patients without matched family donors. In this study, we examined several parameters that have not been studied in detail -- radiation dose, cell dose, age of mice, and maternal and neonatal characteristics of the cord blood donor -- that affect engraftment of cord blood in non-obese diabetic-severe combined immunodeficient (NOD--scid) mice. Engraftment, measured using flow cytometry analyses of human CD45(+) cells, was highest in 400 cGy-treated mice. Successful engraftment was demonstrated up to 6 months, with a mean engraftment of 31% (range 0--67%) of human cells in recipient bone marrow. Engraftment was skewed to B lymphocytes. The radiation dose of 350 cGy resulted in superior survival of the murine recipients compared with 400 cGy (P = 0.03). The sex of the NOD--scid recipients had a significant effect on survival (female superior to male, P = 0.01), but not on engraftment. There were high levels of variability among different cord units and among animals injected with the same cord unit. This variability may limit the clinical usefulness of the NOD--scid mice as hosts for the quantification of human stem cells.
Ballen
K K
KK
University of Massachusetts Cancer Center, Worcester, MA, USA. ballenk@ummhc.org
Valinski
H
H
Greiner
D
D
Shultz
L D
LD
Becker
P S
PS
Hsieh
C C
CC
Stewart
F M
FM
Quesenberry
P J
PJ
D000818:Animals; D005260:Female; D005312:Fetal Blood; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D011247:Pregnancy; D011379:Prognosis; D011829:Radiation Dosage; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome