![]() In conclusion, we demonstrated for the first time that allogeneic HSCs from a different inbred strain can compete for niches in the BM compartment of NSG mice. Using this novel NSG transplantation model, we will be able to study the effects of low dose in vivo X-ray exposure on the long-term fate of HSCs, without the requirement of prior radio-ablation of the recipient, and thus leaving the recipient’s BM microenvironment uncompromised. Also, in vivo irradiated HSCs showed long-term engraftment, although overall white blood cell (WBC) donor chimerism was lower compared with non-irradiated HSCs. All transplanted NSG mice showed long-term myeloid and lymphoid cell chimerism. We transplanted allogeneic HSCs constitutively expressing the mCherry fluorescent marker into age-matched NSG mice and assessed donor chimerism 6 months post-transplantation. Here, we present data on the transplantation of HSCs into NOD scid gamma (NSG) mice to achieve long-term engraftment without prior conditioning. Nevertheless, NOD scid mice have a significantly altered life span due to early development of thymic lymphomas, which compromises the ability to study the long-term fate of exogenous HSCs and their progeny. Nat Biotechnol 2010 28: 275–280.Scid hematopoietic stem cells (HSCs) have an intrinsic defect in their maintenance within the bone marrow (BM) niche which facilitates HSC transplantation without the absolute requirement of prior conditioning. Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Saito Y, Uchida N, Tanaka S, Suzuki N, Tomizawa-Murasawa M, Sone A et al. Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-beta2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells. Kerbauy DM, Lesnikov V, Torok-Storb B, Bryant E, Deeg HJ. Engraftment of NOD/SCID-beta2 microglobulin null mice with multilineage neoplastic cells from patients with myelodysplastic syndrome. Thanopoulou E, Cashman J, Kakagianne T, Eaves A, Zoumbos N, Eaves C. NOD/SCID mice transplanted with marrow from patients with myelodysplastic syndrome (MDS) show long-term propagation of normal but not clonal human precursors. Eur J Haematol 1998 61: 93–99.īenito AI, Bryant E, Loken MR, Sale GE, Nash RA, John Gass M et al. Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodeficient (TG-SCID) mice expressing human GM-CSF and IL-3. Kim DK, Kojima M, Fukushima T, Miyasaka M, Nakauchi H. A robust xenotransplantation model for acute myeloid leukemia. Sanchez PV, Perry RL, Sarry JE, Perl AE, Murphy K, Swider CR et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B et al. In an attempt to improve on these models, we tested whether the increased deficiency in natural killer cell function in NSG mice might improve the myeloid cell engraftment of MDS samples with low myeloblast counts and provide a useful pre-clinical model of low-risk MDS. ![]() To date, there has been only limited success in establishing a robust xenograft model of low-risk myelodysplastic syndromes (MDS) despite the use of a variety of immune deficient and transgenic mice. 1, 2 Carroll and colleagues 3 have recently reported in Leukemia the engraftment of human acute myeloid leukemia cells in the bone marrow of NSG mice, suggesting that NSG mice may be more permissive to human malignant myeloid cell engraftment than the previous xenograft hosts. NSG mice have severe T- and B-cell impairment, as well as a complete absence of natural killer-cells. NOD/SCID IL2Rgamma-c null mice (NSG) represent the latest iterative attempt to limit both the innate and acquired immune function in mice, thus preventing immune surveillance during xenografting. The development of increasingly immunocompromised mice has allowed for improved engraftment of human tissue in xenograft hosts. ![]()
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