Implantation and maintenance of functional human bone marrow in SCID-hu mice

Abstract

Human fetal bone fragments implanted in the immunodeficient C.B-17 scid/scid (SCID) mouse were shown to sustain active human hematopoiesis in vivo. Human progenitor cell activity was maintained for as long as 20 weeks after implantation and was associated with multilineage differentiation in the engrafted bone. Thus, the bone implants provided stem cells as well as the microenvironment requisite for their long- term maintenance and multilineage differentiation. Administration of human erythropoietin (Epo) stimulated human erythropoiesis in human bone implants. This animal model may facilitate direct analysis of a wide variety of physiologic and pathologic conditions of human bone marrow (BM) in vivo.

Stem cell factor enhances the survival of irradiated human bone marrow maintained in SCID mice

“…Subpopulations of Ly5.1' murine hematopoietic cells and other nonreactive (Ly5.1-, CD45-) cells were observed in all bone marrow samples. Fetal bone graft size and cell yield was variable, as previously reported [6]. The bone marrow cell yield per fetal bone fragment ranged from 250,000 to 13,950,000 and did not correlate with treatment group.…”

“…SCID/Hu mice were constructed and maintained by Systemix, Inc. (Palo Alto, CA) as previously described [6]. Briefly, human fetal iliac wings, femurs and tibias were obtained at 17 to 22 weeks gestational age, cut into fragments (-5 x 5 x 10 mm), and implanted subcutaneously in six to eight week old SCID mice.…”

“…In order to have enough cells to plate colony forming assays in triplicate, bone marrow cell suspensions from all five mice in each treatment group were pooled. The effect of SCF on colony forming unit survival per graft is not reported because, unlike mouse femurs, the human fetal bone fragment sizes are markedly heterogeneous [6]. Instead, results are reported as surviving colony forming units per 20,000 total bone marrow cells (raw data) and colony forming units per 20,000 human bone marrow cells (normalized data).…”

“…Recently, the study of the human hematopoietic system has been facilitated by the availability of immunodeficient mice that support active human hematopoiesis (SCID/Hu mice) [6]. This in vivo model provides a useful system for analyzing the physiology of human hematopoiesis.…”

Sustained proliferation, multi‐lineage differentiation and maintenance of primitive human haemopoietic cells in NOD/SCID mice transplanted with human cord blood

“…Thus, multi-lineage haemopoiesis has been successfully established by in utero transplantation of fetal lambs (Zanjani et al, 1994) and dogs (Omori et al, 1996), by direct injection of human fetal tissues (e.g. bone or fetal liver) previously implanted into mice with the severe combined immunodeficiency (SCID) mutation (the so-called SCID-hu mouse model) (McCune et al, 1988;Kyoizumi et al, 1992;Fraser et al, 1995), and by simple intravenous injection of various types of myeloablated immunodeficient mice (e.g. SCID mice, BEIGE-NUDE-Xid mice [bnx mice], and nonobese-diabetic-SCID [NOD/SCID] mice) (Kamel-Reid & Dick, 1988;Lapidot et al, 1992;Nolta et al, 1994;Lowry et al, 1996;Pflumio et al, 1996;Larochelle et al, 1996;Cashman et al, 1997).…”