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Human hematopoiesis in SCID mice implanted with human adult cancellous bone
JS Sandhu, BR Clark, EL Boynton, H Atkins, H Messner, A Keating and N Hozumi
Department of Surgery, University of Toronto, Ontario, Canada.
The persistence of hematopoietic cells from human adult cancellous bone
fragments implanted subcutaneously into CB-17 scid/scid mice was studied.
Recipient mice received either no pretreatment (control group) or
pretreatment with 3 Gy total-body irradiation and anti-asialo GM1 sera
(ASGM1; pretreated group) before implantation. Pretreated severe combined
immunodeficient (SCID) mice implanted with human bone were subsequently
given ASGM1 every 7 days for the duration of the experiments. At 12 weeks
postimplantation, flow cytometry of cells from pretreated and control
animal tissues detected human CD45+ cells in the mouse spleen (mean, 7.8%
and 3.4% positive cells, pretreated and control animals, respectively),
bone marrow (BM; mean, 16.5% and 4.8% positive cells, respectively), and
blood (mean, 5.5% and < 2% positive cells, respectively), and in the
implanted human bone (73% and 8.9% positive cells, respectively). At 12
weeks, pretreated mice had human granulocyte-macrophage colony-forming
cells (GM-CFC) and burst-forming units-erythrocyte (BFU-E) in the implanted
human bone in the murine BM and in some of the spleens. The spleens also
had extensive infiltration of human B cells and macrophages. Mean serum
levels of human IgG in pretreated animals were 14 micrograms/mL during
weeks 6 to 12, compared with trace levels (< 1 microgram/mL) in control
mice. Bone from patients with acute myeloblastic leukemia (AML) was also
implanted in pretreated SCID mice, and retrieved at 8 weeks for analysis.
Comparison of preimplantation and implanted samples showed that the
original histology was maintained, and massive infiltration of human CD68+
cells was observed in the mice spleens and BM. Implantation of AML bone in
SCID mice facilitates analysis of in situ AML cell interaction with stromal
cells in the leukemic state, and therapies against AML can be tested in
this system, especially the selective killing of AML cells in the presence
of other BM cells. Furthermore, this model requires no exogenous
administration of cytokines to maintain human hematopoiesis with both
normal or AML bone. Because the structure and function of both normal and
diseased human adult bone is maintained, this animal model should
facilitate investigation of both normal human hematopoiesis and
hematopoietic malignancies.
Volume 88,
Issue 6,
pp. 1973-1982,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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