beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function.
Human SCID repopulating cells (SRC) are defined based on their functional ability to repopulate the bone marrow of NOD/SCID mice with both myeloid and lymphoid cell populations. The frequency of SRC in umbilical cord blood cells is 1 in 9.3 x 10(5) mononuclear cells. We report that as few as 8 x 10(4) human cord blood mononuclear cells transplanted into NOD/SCID/B2m(null )mice resulted in multilineage differentiation in the murine bone marrow, revealing a more than 11-fold higher SRC frequency than in NOD/SCID mice. Moreover, as few as 2 to 5 x 10(3) CD34(+) cells recovered from the bone marrow of primary transplanted NOD/SCID mice were sufficient for engrafting secondary NOD/SCID/B2m(null )mice with SRC, suggesting SRC self-renewal. Thus, by using NOD/SCID/B2m(null )mice as recipients, we established a functional assay for human stem cells capable of engrafting the bone marrow of primary and secondary transplanted immune-deficient mice with SRC, providing a model that better resembles autologous stem cell transplantation.
Kollet
O
O
Department of Immunology, The Weizmann Institute and the Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel.
Peled
A
A
Byk
T
T
Ben-Hur
H
H
Greiner
D
D
Shultz
L
L
Lapidot
T
T
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004195:Disease Models, Animal; D017353:Gene Deletion; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D001613:beta 2-Microglobulin / Q000235:genetics*
D001613:beta 2-Microglobulin