Phone: 207-288-6883 Good platform for screening efficacy of genetically modified stem cells (. Used to deliver personalized information and tailor communications. Hu-CD34+ humanized mice dosed with 10 mg/kg MK -4166 (humanized IgG1 anti -huGITR) when SKMEL -5 tumors reached 130 mm 3. Long term studies are possible in huNOG mice, with literature reports of stable engraftment and hematopoiesis for one year or more. HuCD34-NCG mice are an ideal in vivo platform to evaluate the effectiveness of compounds modulating the human immune system. Our inventory has CD34+ mice available for immediate shipment to your facility or efficacy study enrollment at ours. We further characterized in detail the development of human blood lineage cells in adult NSG recipients injected with expanded CD34 + CD133 + cells. Isotype Control MK-4166. To confirm that your company is covered or for new license inquiries, please contact: techtran@jax.org. This valuable off-the-shelf resource can save your project more than 6-12 weeks time. Product Overview. The models readily available include: NSG, NSG-SGM3, NSG-IL15; custom models are available on-demand (for a list of NSG variants, click here). Companies and for-profit entities require a no-fee license prior to shipping. These NSG mice combine the features of the NOD background, the SCID, and IL2 receptor gamma chain deficiency (IL2Rg null). Hu-CD34-NSG™ and hu-CD34-SGM3 are ideal for long-term in vivo studies in the areas of immunology, immuno-oncology, infectious diseases and more -since their lifespan after CD34+ engraftment is over 12 months. Rev. NSG™ mice engrafted with human PBMCs (hu-PBMC), best-suited for short-term studies targeting mature T cells, are available upon request. (A) Strategy to study the immunogenicity of hiPSC derivatives. CD34+ Hu-NSG were enriched from human cord blood using immune-magnetic beads (CD34+ selection kit; Miltenyi Biotec Inc., Auburn, CA, USA). Experimental Timeline for JAX® Hu-NSG 30 CD34+ cells engrafted in 3 week old female mice Human T cells appear Human B cells appear Whole body irradiation Tail vein injection Mouse Age 3 weeks 12 weeks 15 weeks In Vivo Pharmacology Services | Hu-CD34-NSG™ and hu-CD34-SGM3 are ideal for long-term in vivo studies in the areas of immunology, immuno-oncology, infectious diseases and more -since their lifespan after CD34+ engraftment is over 12 months. H1299-luc cells were implanted subcutaneously in humanized mice (at week 6–8 after humanization). PDX tumors were engrafted into partially HLA-matched hu-NSG-SGM3 mice at 9 weeks post engraftment. All mice ship with >25% hu-CD45+ cells in the peripheral blood. With the hu-IL15, you can test the efficacy of NK-cell mediated therapeutics, including ADCC. Many companies already have a license that includes engrafted NSG™ mice. Female NSG™ mice are injected with human hematopoietic stem cells (hu-CD34 + ). For more information on using NSG mice and their variants, click here. Newborn NSG were intrahepatically injected with human CD34 + FL cells within 72 h of birth and intravenously infected with HCV Humanized mice were able to support HCV infection and demonstrated clinical symptoms and immune responses (innate and adaptive) commonly observed in … NSG mice mainly exhibited incidental findings in lungs, kidneys, testes, and adrenal glands. There are many mouse models that reflect GvHD on an interspecies level. Human CD34+ hematopoietic stem cell-engrafted NSG⢠or NSG⢠variant mice (hu-CD34) develop multi-lineage human immune cells, and are a validated platform for immunology or immuno-oncology efficacy studies, and infectious disease research. Director, Technology Transfer As a result, these NSG mice lack mature T cells, B cells, or functional NK cells and are deficient in cytokine signaling, leading to better engraftment of human HSC and PBMC cells. There is a major obstacle to the evaluation of new human immunotherapies due to a lack of experimental models with a fully functional human immune system. Hu-CD34 NSG models are ideally suited for testing therapeutics with antigen-independent T cell MOA. They further found in mice treated with a single co-transfer of 1,25D 3-DCs along with hu-PBMCs, ... NSG™ mice transplanted with human CD34+ … HTLV-1–infected or mock CD34 + HPCs (2 × 10 5) were injected into sublethally irradiated (25 rads) 1- to 2-day-old NSG mice (The Jackson Laboratory) intrahepatically to generate HTLV-1-HU-NSG and mock HU-NSG mice as described previously. CD34+ humanization process. We assessed whether CD34 + CD133 + cells were present in the reconstituted mice. NOG mice engrafted with human CD34+ hematopoietic stem cells (HSCs) stably develop multiple cell lineages by 12-16 weeks post-injection. The lack, or late onset, of graft-versus-host disease (GvHD) in humanized mice make them ideal for long-term … Any mouse with more than 25% hCD45 + cells is considered successfully humanized. You may decline these cookies although certain areas of the site may not function without them. 2005). Email: Peter.Wells@jax.org. Cells were implanted subcutaneously into the right-hind flank of female human CD34 + reconstituted NSG mice 20–24 weeks old (The Jackson Laboratory, Bar Harbor, Maine, USA). NSG™ mice are available to non-profit research institutions under an MTA. A mouse model expressing human cells (humanized) is a beneficial tool to study diseases and develop therapeutics. Companies and for profit entities require a license prior to shipping. Multi-lineage hematopoiesis occurs within 12 weeks. Get experimental data up to 80% faster with PDX Live™ tumors. We are utilizing humanized CD34 + NSG TM mice (Hu-NSG) from The Jackson Laboratory for a range of HSC-PDX evaluations. CD34+ hu-NSG murine model was generated via perinatal intrahepatic injection of human CD34+ fetal liver cells into NSG mice after preconditioning irradiation. 3. •Hu-SRC-SCID mice: scid mice that have been sublethally irradiated and injected with hematopoietic stem cells (HSC) –scid repopulating cells (SRC) = CD34+ cells •SCID-Hu mice: scid mice that have been engrafted with human fetal liver and thymus under the renal capsule –BLT with autologous CD34+ cells from liver LD Shultz, et.al., 2007. The NSG-Tg(Hu-IL15) mice were generated using a BAC containing the human IL15 gene, and express a physiological level of human IL15 (7.1 ± 0.3 pg/ml). Study-ready cohorts of inventoried humanized CD34+ mice are readily available for shipment to your institution or for enrollment in customized drug efficacy studies executed by our experienced Ph.D. level scientists from JAX In Vivo Services. Used to deliver personalized information and tailor communications. 2010). with 1.74±0.57 x 105 (mean±SD) CD34+ cells. Start your research today with our readily-available models. Therefore, the development of humanized experimental models is an unmet need in immunotherapy research. Researchers at academic institutions are approved to order engrafted NSG mice. We believe that this preservation contributes to the superior multi-lineage hematopoiesis in hu NSG mice as compared to other hu mouse models. NSG branded mice are among the most immunodeficient described to date. The humanized NSG™ mice are maintained in an intermediate barrier. Days following start of treatment. Our expertise includes: Evaluation of combination therapies of an immunotherapy plus a targeted agent APT070‐treated islets were transplanted under the kidney capsule of hu‐NSG mice. A, Comparison of the growth of subcutaneous tumors in humanized (Hu-NSG), using fresh CD34 + HSC from multiple donors of different HLA types and nonhumanized (NSG) mice. We use cookies to personalize our website and to analyze web traffic to improve the user experience. HuCD34-NCG Mouse Model. All mice ship with >25% huCD45+ cells in the peripheral blood. Creative Biolabs offers a variety of humanized animal models (CD34+ Humanized Mouse Model and PBMC Humanized Mouse Model) for CAR-T preclinical therapy evaluation. Methods:We provide a direct comparison of check-point inhibitors evaluation in NSG and NSG-SGM3 mice engrafted with CD34+human hematopoietic progenitor cells (HPCs) from the same donor and implanted with PDX tumors. CD34+ hu-NSG-SGM3 are best for therapeutics with T cell and myeloid cell dependent MOA, including those that target AML. JAX has been the pioneer of developing cutting-edge immunodeficient strains such as the NSG™ models and its variants to enable powerful research. NSG mice were irradiated 1–2 days after birth with 1 Gy and subsequently injected intrahepatically (i.p.) We distribute NSG™ mice under an agreement with the NIH. Hu CD34 Hematopoietic Stem Cell Reconstitution Mouse Model. For example, NSG™engrafted models offer the longest research span, over 12 months with a functional human immune system displaying T-cell dependent inflammatory responses with no donor cell immune reactivity towards the host. Looking for blogs, on-demand videos and livestreams that JAX about Humanized mice? For more information on using NSG mice and their variants, click here. Used to analyze web traffic to improve the user experience. NSG branded mice lack mature T cells, B cells, and natural killer (NK) cells. Female mice are injected with human hematopoietic stem cells (hu-CD34+). 0 200 400 600 800 1000. Many companies already have a license that includes engrafted NSG⢠mice. You may decline these cookies although certain areas of the site may not function without them. 2005). We use cookies to personalize our website and to analyze web traffic to improve the user experience. Nat. NSG™ mice engrafted with human CD34+ hematopoietic stem cells (hu-CD34) demonstrate robust multi-lineage engraftment of human immune cell populations including very good T cell maturation and function. The HuCD34-NCG mouse from Charles River is a study-ready mouse model with a human-like immune system, created by adoptive transfer of CD34 + stem cells. The latest health report of the mouse room can be viewed here. 0 7 14 21 28 35 42 49. The NOD scid gamma (NSG™) recipient mouse, developed by JAX Professor Lenny Shultz, has been shown to support greater engraftment of human hematopoietic stem cells (hu-CD34+ cells) than all other currently available strains (McDermott et al. Hu NSG PDX mice were either treated or not with 10 mg/kg pembrolizumab at day 31 after xenograft with liposarcoma, followed by 5 mg/kg pembrolizumab at days 36, 41, 46, 51, and 56 after xenograft, as indicated. NSG Mouse Also Provides Highly Immunodeficient Mouse Model Human cell reconstitution in adult NSG mice reconstituted with expanded CD34 + CD133 + cells. Humanized CD34+ mice are supreme in vivo models to study immunology, infectious diseases, and more. Visit our humanized mouse content hub for all the latest JAX humanized mouse resources. Human fetal liver/thymus and autologous CD34 + fetal liver cells were transplanted into NSG mice to generate Hu-mice. Tumor Volume mm. Another purpose of this study was to assess the spectrum of histopathological lesions and identify the main causes of morbidity and mortality in young NSG mice and CD34+ HSC hu-NSG mice. The hosts for hu-CD34 and hu-PBMC models are NOD SCID gamma (NSG) mouse (JAX laboratories). Applications. 18 Mice were housed under specific pathogen–free conditions. Graft versus Host Disease (GvHD) is mainly caused by T cells from the donor that attack recipient cells. Eight weeks after the transplantation, hu-NSG mice were subjected to sepsis induced Eight weeks after the transplantation, hu-NSG mice were subjected to sepsis induced by endotoxemia—Escherichia coli lipopolysaccharide (LPS)—or by cecal ligation and puncture (CLP). Blood collected from humanized NSG and NOD/SCID mice between 9 and 18 weeks after receiving human CD34 + cells or CD34 + cells plus human thymic tissue was analyzed for human platelet reconstitution. human cord blood CD34+ cells. Our study-ready NSG⢠variant mice are the most versatile immunodeficient strains. Human CD34+ hematopoietic stem cell-engrafted NSG™ mice (hu-CD34) develop multi-lineage human immune cells, and are a validated platform for studying hematopoiesis, infectious disease and cancer. Please refer to our privacy policy for more information. Engraftment of mature human white blood cells (hCD45 +) is confirmed 12 weeks after injection. We routinely generate cohorts of NSG™ mice engrafted with hu-CD34+ cells which offer improved humoral and mucosal immunity. We examine each humanized mouse for the presence of huCD45+ cells and murine CD45+ cells (mCD45) in the mouse peripheral blood by flow cytometry 12 weeks post-engraftment. Hu-CD34+ mice produced by injecting CD34+ hematopoietic stem cells (hu-CD34) demonstrate robust multi-lineage engraftment of human immune cell populations including very good T cell maturation and function for long-term studies. Indeed, BRG mice transplanted with fetal liver-derived sorted CD34 + CD38- cells experienced a decrease of the percentage of CD34 + CD38- cells already at 6 weeks of age [ 21 ]. 2005) and our own experience support the 12-week window as being required for functional development of mature T cells. Consistent with our previous results, 8–10 humanized mice had high levels of human CD45 + cells in peripheral blood mononuclear cells (PBMCs; Figure 1 A-B), including CD3 + T cells and … Why do we need humanized mice? Any mouse with more than 25% hCD45+ cells is considered successfully humanized. Engraftment of mature human white blood cells (hCD45+) is confirmed 12 weeks after injection. Human lymphocytes are present in peripheral blood, bone marrow, thymus and spleen. To confirm that your company is covered or for new license inquiries, please contact: Peter Wells Onco-Hu® Models are a robust platform for efficacy testing of novel immunotherapies targeting various immune cells, including T cells, myeloid cells, and NK cells. Transplanting human CD34 + HSCs results in the huNOG mouse with stable multiple cell lineages within 12-16 weeks, human lymphocytes present in peripheral blood, bone marrow, thymus and spleen, and a long term model, with stable engraftment and hematopoiesis for one year or more. Postbacc, Ph.D., and Postdoctoral Programs. Engraftment is stable for over one year without graft-versus-host disease. Tumors were isolated from Ctrl HG-Hu-NSG PDX mice, LG-Hu-NSG PDX mice, or HG-Hu-NSG PDX mice at different times, as indicated. Please refer to our privacy policy for more information. Study-ready cohorts of inventoried humanized mice are readily available for shipment to your institution or for enrollment in customized drug efficacy studies executed by our In Vivo Services scientists. The present study focuses on CD34+ HSC humanized NSG (hu-NSG) mice, a model in which T and B cell engraftment is generally successful, though without consistent immunoglobulin (Ig) class switching and only IgM production by B cells.18,40,48 Hu-NSG mice … The Jackson Laboratory CD34+ cells were isolated from human cord blood with immuno-magnetic beads (CD34 MicroBead Kit; Miltenyi Biotec) with a purity of 92.8±5.9% (n=25) and cryopreserved in FBS and 10% DMSO until use. We histologically examined 3- to 6-month-old NSG mice, naïve or engrafted with CD34 + human hemopoietic stem cells (HSC), and employed a quantitative immunohistochemical approach to identify human and murine cell compartments, comparing the results with the FACS data. Moreover, no IFN-γ–secreting cells were detected in any of the control mice or in EBV-infected hu-NSG mice reconstituted with HLA-A2 + matching (n = 2) or nonmatching (n = 8) CD34 + cells against the used peptide pools ex vivo. Anti-hu GITR mimics many features of mDTA -1 in Hu-CD34+ NSG HIS tumor model. Cord Blood CD34+ Hematopoietic Stem Cells for Immune-Oncology Studies ... outlines a protocol for generating hu-manized mice by transplanting cord blood huCD34+ HSCs. Engraftment is stable for over one year without graft-versus-host disease. RESEARCH MODELS. Highly immunodeficient animals are required to support the engraftment of human cells. Immunodeficient mice (NSG) of 4–6 weeks old were engrafted with UCB‐derived CD34 + stem cells and, after 16 weeks, a significant percentage of human CD45 + cells was detectable in the blood of these mice (Supplementary Figure 2). Published reports (Ishikawa et al. Female NSG™ mice are injected with human hematopoietic stem cells (hu-CD34+). The engrafted human hematopoietic stem cells have been tested to be free of HIV, HBV, HCV and LCMV (lymphocytic choriomeningitis virus). CD4+ and CD8+ T cells are present in circulation and other tissues (Shultz et al. Used to analyze web traffic to improve the user experience. The NSG mouse (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson Laboratory, which carries the strain NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ. The mice are created by first sub-lethally irradiating NSG™ or NSG™-SGM3 mice at 3–4 weeks of age, followed by subsequent tail vein injection of human CD34 + HSCs isolated from cord blood. Successful humanization of each mouse is quantified from mouse peripheral blood via flow cytometry using anti- hu-CD45+ and anti-murine CD45+, approximately 2 months post-engraftment, when mature T-cells develop (Ishikawa et al. Postbacc, Ph.D., and Postdoctoral Programs, The latest health report of the mouse room can be viewed here. Engraftment of mature human white blood cells (hCD45+) is confirmed approximately 2 months after injection.