HUMAN HEMATOPOIESIS IN SCID MICE IMPLANTED WITH HUMAN ADULT CANCELLOUS BONE

The persistence of hematopoietic cells from human adult cancellous bon e fragments implanted subcutaneously into CB-17 scid/scid mice was stu died. Recipient mice received either no pretreatment (control group) o r pretreatment with 3 Gy total-body irradiation and anti-asialo GM1 se ra (ASGM1; pretreated group) before implantation. Pretreated severe co mbined immunodeficient (SCID) mice implanted with human bone were subs equently given ASGM1 every 7 days for the duration of the experiments. At 12 weeks postimplantation, Row cytometry of cells from pretreated and control animal tissues detected human CD45(+) cells in the mouse s pleen (mean, 7.8% and 3.4% positive cells, pretreated and control anim als, respectively), bone marrow (BM; mean, 16.5% and 4.8% positive cel ls, respectively), and blood (mean, 5.5% and <2% positive cells, respe ctively), and in the implanted human bone (73% and 8.9% positive cells , respectively). At 12 weeks, pretreated mice had human granulocyte-ma crophage colony-forming cells (GM-CFC) and burst-forming units-erythro cyte (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 a nimals were 14 mu g/mL during weeks 6 to 12, compared with trace level s (<1 mu g/mL) in control mice. Bone from patients with acute myelobla stic leukemia (AML) was also implanted in pretreated SCID mice, and re trieved at 8 weeks for analysis. Comparison of preimplantation and imp lanted samples showed that the original histology was maintained, and massive infiltration of human CD68(+) cells was observed in the mice s pleens and BM. Implantation of AML bone in SCID mice facilitates analy sis of in situ AML cell interaction with stromal cells in the leukemic state, and therapies against AML can be tested in this system, especi ally the selective killing of AML cells in the presence of other BM ce lls. Furthermore, this model requires no exogenous administration of c ytokines 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 investig ation of both normal human hematopoiesis and hematopoietic malignancie s. (C) 1996 by The American Society of Hematology.