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Blood, Vol. 95 No. 10 (May 15), 2000: pp. 3102-3105

beta 2 Microglobulin-deficient (B2mnull) NOD/SCID mice are excellent recipients for studying human stem cell function

Orit Kollet, Amnon Peled, Tamara Byk, Herzl Ben-Hur, Dale Greiner, Leonard Shultz, and Tsvee Lapidot

From the Department of Immunology, The Weizmann Institute and the Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel; the University of Massachusetts, Worcester MA; and The Jackson Laboratory, Bar Harbor, ME.

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 × 105 mononuclear cells. We report that as few as 8 × 104 human cord blood mononuclear cells transplanted into NOD/SCID/B2mnull mice resulted in mutlilineage 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 × 103 CD34+ cells recovered from the bone marrow of primary transplanted NOD/SCID mice were sufficient for engrafting secondary NOD/SCID/B2mnull mice with SRC, suggesting SRC self-renewal. Thus, by using NOD/SCID/B2mnull 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.


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