The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Development and function of human innate immune cells in a humanized mouse model
Open accessAbstract
Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Species-specific differences between animals and humans cause differences in drug efficacy and toxicity tests in physiology and cell biology31–37.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [34]
In the citing paper
“MITRG mice allow for xenotransplantation and is designed to support human myeloid engraftment.”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Rongvaux et al., 2014
In the citing paper
“Similarly, mice reconstituted with a functional human immune system (humanized mice) can be used for studying the therapeutic effects of nanomedicines against autoimmune diseases such as diabetes, or to harbour patient-derived tumours for preclinical testing of cancer immune nanomedicines95.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [95]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,338
Functions of natural killer cells
Vivier, E., Tomasello, E., Baratin, M., Walzer, T., & Ugolini, S. (2008) · Nature Immunology · doi:10.1038/ni1582 · Cited by 3,943
Of Mice and Not Men: Differences between Mouse and Human Immunology
Mestas, J., & Hughes, C. C. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2731 · Cited by 3,822
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578
Bingle, L., Brown, N. J., & Lewis, C. E. (2002) · The Journal of Pathology · doi:10.1002/path.1027 · Cited by 2,022
van Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763
Blood Monocytes: Development, Heterogeneity, and Relationship with Dendritic Cells
Auffray, C., Sieweke, M. H., & Geissmann, F. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132557 · Cited by 1,745
Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors
Cros, J. F., Cagnard, N., Woollard, K. J., Patey, N., Zhang, S., Sénéchal, B., Puel, A., Biswas, S. K., Moshous, D., Pïcard, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.012 · Cited by 1,320
Nelson, C. M., & Bissell, M. J. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104315 · Cited by 1,153
Flagged first, then by citations
Cited by
Sorted by citations
Cancer nanomedicine: progress, challenges and opportunities
Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.108 · Cited by 5,873
Roles of the immune system in cancer: From tumor initiation to metastatic progression
Gonzalez, H., Hagerling, C., & Werb, Z. (2018) · Genes & Development · doi:10.1101/gad.314617.118 · Cited by 2,111
“In this model, irradiated immune-deficient mice are reconstituted with a human immune system (Rongvaux et al. 2014; Verma et al. 2017)).”
BackgroundiPSC-derived human microglia-like cells to study neurological diseases
Abud, E. M., Ramirez, R. N., Martinez, E. S., Healy, L. M., Nguyen, C. H. H., Newman, S. A., Yeromin, A. V., Scarfone, V. M., Marsh, S. E., Fimbres, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.042 · Cited by 1,154
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
Galluzzi, L., Vitale, I., Warren, S., Adjemian, S., Agostinis, P., Buqué, A., Chan, T. A.-T., Coukos, G., Demaria, S., Deutsch, É., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000337 · Cited by 1,210
The fate and lifespan of human monocyte subsets in steady state and systemic inflammation
Patel, A. A., Zhang, Y., Fullerton, J. N., Boelen, L., Rongvaux, A., Maini, A. A., Bigley, V., Flavell, R. A., Gilroy, D. W., Asquith, B., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170355 · Cited by 946
“10 week-old MISTRG mice (Deng et al., 2015; Rongvaux et al., 2014) were used for adoptive transfer experiments described below.”
BackgroundMethodInfluentialSelf-citationPhagocytosis: An Immunobiologic Process
Gordon, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.026 · Cited by 902
“This pathway has been targeted to prevent clearance of human erythroid precursors in humanized mice (Rongvaux et al., 2014).”
BackgroundConsensus guidelines for the detection of immunogenic cell death
Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., Aranda, F., Barnaba, V., Bloy, N., et al. (2014) · OncoImmunology · doi:10.4161/21624011.2014.955691 · Cited by 832
Microenvironmental regulation of therapeutic response in cancer
Klemm, F., & Joyce, J. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.11.006 · Cited by 795
Clinical relevance of tumour-associated macrophages
Pittet, M. J., Michielin, O. A., & Migliorini, D. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00620-6 · Cited by 793
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.008 · Cited by 706
Current hurdles to the translation of nanomedicines from bench to the clinic
Đorđević, S., Gonzalez, M. M., Conejos‐Sánchez, I., Carreira, B., Pozzi, S., Acúrcio, R. C., Satchi‐Fainaro, R., Florindo, H. F., & Vicent, M. J. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-021-01024-2 · Cited by 715
“Relevant approaches include the development of patient-derived xenografts (PDXs), humanized mouse models [193], and genetically engineered mouse models (GEMMs) with aggressive metastasis [194]; however, the development and application of these models remain time-consuming and expensive.”
BackgroundInterrogating open issues in cancer precision medicine with patient-derived xenografts
Byrne, A. T., Alférez, D., Amant, F. C., Annibali, D., Arribas, J., Biankin, A. V., Bruna, A., Budínská, E., Caldas, C., Chang, D. K.-F., et al. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.140 · Cited by 683
Tissue-specific macrophages: how they develop and choreograph tissue biology
Mass, E., Nimmerjahn, F., Kierdorf, K., & Schlitzer, A. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00848-y · Cited by 621
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638
“…stimuli on human microglia is the transplantation of human induced pluripotent stem (iPS) cell-derived haematopoietic progenitor cells (HPCs) into the brain of immunodeficient mice 224 that overexpress human colony-stimulating factor 1 (CSF1), which supports human microglia survival 225,226 .”
Humanized Mouse Models of Clinical Disease
Walsh, N. C., Kenney, L. L., Jangalwe, S., Aryee, K., Greiner, D. L., Brehm, M. A., & Shultz, L. D. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100332 · Cited by 585
“Tumor growth was increased in Hu-SRC-SCID MISTRG tumor-bearing mice when compared to Hu-SRC-SCID NSG tumor bearing mice suggesting macrophages/ myeloid cells promote tumor growth (97).”
BackgroundMethodRegulation of macrophage immunometabolism in atherosclerosis
Koelwyn, G. J., Corr, E. M., Erbay, E., & Moore, K. J. (2018) · Nature Immunology · doi:10.1038/s41590-018-0113-3 · Cited by 569
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik, E., Qu, R., Junqueira, C., Kaffe, E., Mirza, H., Zhao, J., Brewer, J. R., Han, A., Steach, H. R., Israelow, B., et al. (2022) · Nature · doi:10.1038/s41586-022-04802-1 · Cited by 543
Patient-derived xenograft models in cancer therapy: technologies and applications
Liu, Y., Wu, W., Cai, C., Zhang, H., Shen, H., & Han, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01419-2 · Cited by 533
“Anthony Rongvaux and colleagues knocked in four genes encoding human macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and thrombopoietin (TPO) to their respective mouse loci to support the development of human innate immune cells, including…”
BackgroundBroad CTL response is required to clear latent HIV-1 due to dominance of escape mutations
Deng, K., Pertea, M., Rongvaux, A., Wang, L., Durand, C. M., Ghiaur, G., Lai, J., McHugh, H., Hao, H., Zhang, H., et al. (2015) · Nature · doi:10.1038/nature14053 · Cited by 499
Humanized mouse models for immuno-oncology research
Chuprin, J., Buettner, H., Seedhom, M. O., Greiner, D. L., Keck, J. G., Ishikawa, F., Shultz, L. D., & Brehm, M. A. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00721-2 · Cited by 423
Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo
Hasselmann, J., Coburn, M. A., England, W., Figueroa Velez, D. X., Kiani Shabestari, S., Tu, C. H., McQuade, A., Kolahdouzan, M., Echeverria, K., Claes, C., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.07.002 · Cited by 380
“present in the MITRG; hCSF1, hCSF2, or Thrombopoietin (hTPO) (Rongvaux et al., 2014), were”
BackgroundGeneration of hypoimmunogenic human pluripotent stem cells
Han, X., Wang, M., Duan, S., Franco, P. J., Kenty, J. H.-R., Hedrick, P., Xia, Y., Allen, A., Ferreira, L. M. R., Strominger, J. L., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902566116 · Cited by 363
Mouse models in oncoimmunology
Zitvogel, L., Pitt, J. M., Daillère, R., Smyth, M. J., & Kroemer, G. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.91 · Cited by 361
Humanized mice in studying efficacy and mechanisms of PD‐1‐targeted cancer immunotherapy
Wang, M., Yao, L., Cheng, M., Cai, D., Martínek, J., Pan, C.-X., Shi, W., Ma, A., White, R. D., Airhart, S. D., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700740r · Cited by 345
Development of Immunotherapy Combination Strategies in Cancer
Yap, T. A., Parkes, E. E., Peng, W., Moyers, J. T., Curran, M. A., & Tawbi, H. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1209 · Cited by 352
Joshi, N., Walter, J. M., & Misharin, A. V. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.01.005 · Cited by 307
The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes
Pearson, J. A., Wong, F. S., & Li, W. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.08.019 · Cited by 320
Humanized Mice for the Study of Immuno-Oncology
Rochère, P. D. L., Guil‐Luna, S., Decaudin, D., Azar, G. A., Sidhu, S., & Piaggio, E. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.07.001 · Cited by 292
Claus, C., Ferrara, C., Xu, W., Sam, J., Lang, S., Uhlenbrock, F., Albrecht, R., Herter, S., Schlenker, R., Hüsser, T., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5989 · Cited by 268
“No immune cell accumulation in the liver occurred; however, the low efficiency of myeloid cell engraftment of the HSC-NSG mice model (34) may not completely reflect a fully immunocompetent setting.”
BackgroundReinisch, A., Etchart, N., Thomas, D., Hofmann, N., Frühwirth, M., Sinha, S., Chan, C. K. F., Senarath-Yapa, K., Seo, E. Y., Wearda, T. L., et al. (2014) · Blood · doi:10.1182/blood-2014-04-572255 · Cited by 270
Patient-derived xenograft (PDX) models in basic and translational breast cancer research
Dobrolecki, L. E., Airhart, S., Alférez, D., Aparicio, S. A. J. R., Behbod, F., Bentires‐Alj, M., Brisken, C., Bult, C. J., Cai, S., Clarke, R. B., et al. (2016) · Cancer and Metastasis Reviews · doi:10.1007/s10555-016-9653-x · Cited by 272
McIntosh, B. E., Brown, M. E., Duffin, B. M., Maufort, J. P., Vereide, D. T., Slukvin, I. I., & Thomson, J. A. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.12.005 · Cited by 262
“Two recent studies report limited success in engrafting human HSCs into nonmyeloablated NSGhosts, but the chimerism achieved in the peripheral blood was modest (an average of 3% ± 3% and 18.3% ± 13”
BackgroundInfluentialBain, C. C., & MacDonald, A. S. (2022) · Mucosal Immunology · doi:10.1038/s41385-021-00480-w · Cited by 266
Chen, H.-M., van der Touw, W., Wang, Y. S., Kang, K., Mai, S., Zhang, J., Alsina‐Beauchamp, D., Duty, J. A., Mungamuri, S. K., Zhang, B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97570 · Cited by 254
“STEMCELL Technologies) as previously described (73).”
Humanized immune system mouse models: progress, challenges and opportunities
Allen, T. M., Brehm, M. A., Bridges, S. H., Ferguson, S. E., Kumar, P., Mirochnitchenko, O., Palucka, K., Pelanda, R., Sanders-Beer, B. E., Shultz, L. D., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0416-z · Cited by 259
Tumor-on-a-chip: from bioinspired design to biomedical application
Liu, X., Fang, J., Huang, S., Wu, X., Xie, X., Wang, J., Liu, F., Zhang, M., Peng, Z., & Hu, N. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00277-8 · Cited by 246
Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish
Yan, C., Brunson, D. C., Tang, Q., Do, D., Iftimia, N. A., Moore, J. C., Hayes, M. N., Welker, A. M., Garcia, E. G., Dubash, T. D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.004 · Cited by 242
Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap
Morton, J. J., Bird, G. A., Refaeli, Y., & Jimeno, A. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1260 · Cited by 249
“In an effort to refine expression of these critical cytokines Rongvaux and colleagues generated Rag 2 / -Il2gnull mouse strains featuring targeted knock-ins of the human genes encoding M-CSF, IL3, GM-CSF, and Thpo (36).”
BackgroundColonic macrophage polarization in homeostasis, inflammation, and cancer
Isidro, R. A., & Appleyard, C. B. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00123.2016 · Cited by 238
Vannini, N., Campos, V., Girotra, M., Trachsel, V., Rojas-Sutterlin, S., Tratwal, J., Ragusa, S., Stefanidis, E., Ryu, D., Rainer, P. Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.02.012 · Cited by 218
Reinisch, A., Thomas, D., Corces, M. R., Zhang, X., Gratzinger, D. A., Hong, W., Schallmoser, K., Strunk, D., & Majeti, R. (2016) · Nature Medicine · doi:10.1038/nm.4103 · Cited by 229
“Pettway, G.J. et al. Anabolic actions of PTH (1-34): use of a novel tissue engineering model to investigate temporal effects on bone.”
BackgroundKhan, A. O., Rodriguez-Romera, A., Reyat, J. S., Olijnik, A.-A., Colombo, M., Wang, G., Wen, W. X., Sousos, N., Murphy, L. C., Grygielska, B., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0199 · Cited by 230
“Keywords (3-10): stroma, hematopoiesis, myelofibrosis, leukemia, megakaryocyte, microtissue, bone marrow fibrosis .”
Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease
Lewcock, J. W., Schlepckow, K., Di Paolo, G., Tahirovic, S., Monroe, K. M., & Haass, C. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.029 · Cited by 221
Animal models to study acute and chronic intestinal inflammation in mammals
Jiminez, J. A., Uwiera, T. C., Inglis, G. D., & Uwiera, R. R. E. (2015) · Gut Pathogens · doi:10.1186/s13099-015-0076-y · Cited by 220
“A number of researchers have attempted to create ‘humanized’ mice, which either have human genes knocked into their genomes, or have established a human microbiome in germ-free mice via the transplantation of bacteria within human fecal material to create models potentially more applicable to human diseases [65, 66].”
BackgroundLee, J. W., Komar, C. A., Bengsch, F., Graham, K. L., & Beatty, G. L. (2016) · Current Protocols in Pharmacology · doi:10.1002/cpph.2 · Cited by 212
“While the development of patient-derived xenograft tumor models (Hidalgo et al., 2014) and humanized mice (Rongvaux et al., 2014) has made it possible to preserve many features of tumor heterogeneity and to introduce human leukocyte populations, respectively, these models are challenging…”
BackgroundSanmamed, M. F., Chester, C., Melero, I., & Kohrt, H. E. K. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw041 · Cited by 206
“The infiltrating cells displayed a M2 polarized phenotype [56].”
BackgroundMelanoma models for the next generation of therapies
Patton, E. E., Mueller, K. L., Adams, D. J., Anandasabapathy, N., Aplin, A. E., Bertolotto, C., Bosenberg, M., Ceol, C. J., Burd, C. E., Chi, P., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.01.011 · Cited by 219
“Once engrafted with human CD34+ hematopoietic stem cells, these models are permissive for development of NK cells, macrophages, and monocytes, which have proved challenging to reconstitute in other systems (Rongvaux et al., 2014).”
BackgroundBiomaterials for vaccine-based cancer immunotherapy
Zhang, R., Billingsley, M. M., & Mitchell, M. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.10.008 · Cited by 204
Cella, M., Gamini, R., Sécca, C., Collins, P. L., Zhao, S., Peng, V., Robinette, M. L., Schettini, J. L., Zaitsev, K., Gordon, W., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0425-y · Cited by 195
The development and improvement of immunodeficient mice and humanized immune system mouse models
Chen, J., Liao, S., Xiao, Z., Pan, Q., Wang, X., Shen, K., Wang, S., Yang, L., Guo, F., Liu, H., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1007579 · Cited by 209
“SIRPa inhibits the phagocytosis of macrophages physiologically (110) and plays an important role in the maintenance of hematopoietic stem cells, red blood cells, and platelets (101).”
BackgroundResultAHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice
Goettel, J. A., Gandhi, R., Kenison, J. E., Yeste, A., Murugaiyan, G., Sambanthamoorthy, S., Griffith, A. E., Patel, B., Shouval, D. S., Weiner, H. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.082 · Cited by 191
“Over the past decade immunodeficient mice have been developed that are capable of engrafting human immune cells (Rongvaux et al., 2014; Shultz et al., 2005; Traggiai et al., 2004).”
BackgroundTumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy
Somasundaram, R., Connelly, T., Choi, R., Choi, H., Samarkina, A., Li, L., Gregorio, E., Chen, Y., Thakur, R., Abdel‐Mohsen, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20600-7 · Cited by 184
Distinct developmental pathways from blood monocytes generate human lung macrophage diversity
Evren, E., Ringqvist, E. E., Tripathi, K. P., Sleiers, N., Rives, I. C., Alisjahbana, A., Gao, Y., Sarhan, D., Halle, T., Sorini, C., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.12.003 · Cited by 194
“MISTRG mice support the reconstitution of a human blood monocyte and lung macrophage compartment after transplantation with human CD34 hematopoietic stem and progenitor cells (HSPCs) (Rongvaux et al., 2014; Willinger et al., 2011b).”
InfluentialKit Regulates HSC Engraftment across the Human-Mouse Species Barrier
Cosgun, K. N., Rahmig, S., Mende, N., Reinke, S., Hauber, I., Schäfer, C., Petzold, A., Weisbach, H., Heidkamp, G. F., Purbojo, A., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.06.001 · Cited by 186
“, 2007), and newborn BRg or NSG are successfully used for the generation of humanized mice harboring all components of the innate or adaptive immune system (Ishikawa et al., 2005; Ito et al., 2002; Rongvaux et al., 2014; Traggiai et al., 2004).”
BackgroundImmunobiology of high-grade serous ovarian cancer: lessons for clinical translation
Kandalaft, L. E., Laniti, D. D., & Coukos, G. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00503-z · Cited by 190
Nanoparticle-based medicines in clinical cancer therapy
Wang, S., Cheng, K., Chen, K., Chen, X., Ma, P., Dang, G., Yang, Y., Lei, Q., Huang, H., Yu, Y., et al. (2022) · Nano Today · doi:10.1016/j.nantod.2022.101512 · Cited by 185
Chimeric Antigen Receptor– and TCR-Modified T Cells Enter Main Street and Wall Street
Barrett, D. M., Grupp, S. A., & June, C. H. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500751 · Cited by 182
“More sophisticated models using humanized mice such as the MISTRG strain (immunodeficient mice with transgenic expression of human cytokines such as GM-CSF, M-CSF, IL-3, and thrombopoietin) provide species-specific cytokine support for human cells, allow for improved engraftment of some such cells, and may allow for m…”
MethodCapasso, A., Lang, J., Pitts, T. M., Jordan, K. R., Lieu, C. H., Davis, S. L., Diamond, J. R., Kopetz, S., Barbee, J., Peterson, J. N., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0518-z · Cited by 187
Herndler‐Brandstetter, D., Shan, L., Yao, Y., Stecher, C., Plajer, V., Lietzenmayer, M., Strowig, T., de Zoete, M. R., Palm, N. W., Chen, J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705301114 · Cited by 180
“Human CD34 cells were purified from fetal liver (FL) as described previously (16).”
BackgroundMethodInfluentialLessons from patient-derived xenografts for better in vitro modeling of human cancer
Choi, S. Y. C., Lin, D., Gout, P. W., Collins, C. C., Xu, Y., & Wang, Y. Z. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.009 · Cited by 181
Origin and ontogeny of lung macrophages: from mice to humans
Evren, E., Ringqvist, E. E., & Willinger, T. (2019) · Immunology · doi:10.1111/imm.13154 · Cited by 185
Ioannidis, J. P. A., Kim, B. Y. S., & Trounson, A. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0314-y · Cited by 175
Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice
Das, R., Strowig, T., Verma, R., Koduru, S. V., Hafemann, A., Hopf, S., Kocoglu, M. H., Borsotti, C., Zhang, L., Branagan, A. R., et al. (2016) · Nature Medicine · doi:10.1038/nm.4202 · Cited by 162
“MISTRG and MIS (KI) TRG mice have recently been described 6,7 .”
Macrophages and HIV-1: An Unhealthy Constellation
Sattentau, Q. J., & Stevenson, M. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.02.013 · Cited by 172
“More recent attempts have knocked in human innate immune cell growth factors allowing reconstitution of elements of themyeloid tissue compartment (Rongvaux et al., 2014).”
BackgroundHumanized hemato-lymphoid system mice
Theocharides, A. P. A., Rongvaux, A., Fritsch, K., Flavell, R. A., & Manz, M. G. (2015) · Haematologica · doi:10.3324/haematol.2014.115212 · Cited by 174
“In fact, most next-generation mouse models have been reported to promote improved human myeloid differentiation.26-28,46 As described above, increased support of myelopoiesis is observed in mice that express human TPO.28,46 Furthermore, the number of murine platelets is significantly reduced in TPO mice compared to co…”
BackgroundInfluentialMeraz, I. M., Majidi, M., Meng, F., Shao, R., Ha, M. J., Neri, S., Fang, B., Lin, S. H., Tinkey, P. T., Shpall, E. J., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0874 · Cited by 165
In vitro biomimetic engineering of a human hematopoietic niche with functional properties
Bourgine, P. E., Klein, T., Paczulla, A., Shimizu, T., Kunz, L., Kokkaliaris, K. D., Coutu, D. L., Lengerke, C., Skoda, R. C., Schroeder, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1805440115 · Cited by 153
“Chimeric animal models (10) most closely recapitulate in vivo human physiology, but, in this setting, the niche has remained inaccessible to experimental manipulation and optical observation (11, 12).”
BackgroundA Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma
Krepler, C., Sproesser, K., Brafford, P. A., Beqiri, M., Garman, B., Xiao, M., Shannan, B., Watters, A. K., Perego, M., Zhang, G., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.021 · Cited by 152
“In these models, human CD34+ hematopoietic stem cells are injected to reconstitute human B and T cells in NSG mice (Rongvaux et al., 2014).”
An Integrative Approach to Precision Cancer Medicine Using Patient-Derived Xenografts
Cho, S., Kang, W., Han, J. Y., Min, S., Kang, J., Lee, A., Kwon, J. Y., Lee, C., & Park, H. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2350 · Cited by 152
“Some studies have demonstrated that diverse lineages of functional human immune cells have developed via the infusion of human hematopoietic stem cells, and of human immune and stromal cells, in tumor xenografts (Morton et al., 2015; Rongvaux et al., 2014).”
BackgroundHuman iPSC‐derived microglia: A growing toolset to study the brain's innate immune cells
Hasselmann, J., & Blurton‐Jones, M. (2020) · Glia · doi:10.1002/glia.23781 · Cited by 145
“Furthermore, acquisition of cord blood to isolate the HSPCs requires access to human tissue which is not a simple process for many laboratories.”
BackgroundInfluentialTowards precision oncology with patient-derived xenografts
Zanella, E. R., Grassi, E., & Trusolino, L. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00682-6 · Cited by 154
“Human haematopoiesis in host mice can be supported by the introduction of mesenchymal stromal cells and by the replacement of endogenous murine cytokines with their human equivalents 110-112 , which optimizes mouse humanization but also complicates procedures.”
Wermuth, P. J., & Jiménez, S. A. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0047-4 · Cited by 141
“Another valuable resource that may allow for better evaluation of the role of molecular pathways identified using animal models or in vitro analysis of human monocytes/macrophages is the generation of the MITRG and MISTRG mouse strains carrying human versions of cytokine encoding genes important in human innate immune…”
BackgroundHuman CD56dimCD16dim Cells As an Individualized Natural Killer Cell Subset
Amand, M., Iserentant, G., Poli, A., Sleiman, M., Fiévez, V., Sánchez, I. P., Sauvageot, N., Michel, T., Aouali, N., Janji, B., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00699 · Cited by 141
“We next sought to investigate the existence of CD56dimCD16dim NK cells in a humanized mouse model, in which immunodeficient NSG mice receive human CD34+ hematopoietic stem cells from cord blood after myelosuppression and reconstitute a human immune system within several months (41, 42).”
BackgroundA Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed, M. F., Nie, X., Desai, S., Villarroel‐Espíndola, F., Badri, T., Zhao, D., Kim, A. W., Ji, L., Zhang, T., Quinlan, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0962 · Cited by 140
Zhang, F., Liang, X., Zhang, W., Wang, Y., Wang, H., Mohammed, Y., Song, B., Zhang, R., & Yuan, J. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.09.067 · Cited by 138
“Hypochlorous acid (HOCl) is a strong oxidant that has potent antibacterial properties, playing important roles in the mammalian immune defence system (Dickinson and Chang 2011; Rongvaux et al. 2014; Winterbourn 2008).”
BackgroundInnovations, challenges, and minimal information for standardization of humanized mice
Stripecke, R., Münz, C., Schuringa, J. J., Bissig, K., Soper, B. W., Meeham, T., Yao, L., Santo, J. P. D., Brehm, M. A., Rodríguez, E., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.201708662 · Cited by 138
“Another method to improve and accelerate the regeneration of human T and B cells in HIS mice is the adoptive transfer of geneengineered human DCs from the HSC donor that are long-lived in vivo (Salguero et al, 2014; Daenthanasanmak et al, 2015; Volk et al, 2017).”
BackgroundMethodApplication of Animal Models in Cancer Research: Recent Progress and Future Prospects
Li, Z., Zheng, W., Wang, H., Cheng, Y., Fang, Y., Wu, F., Sun, G., Sun, G., Lv, C., & Hui, B. (2021) · Cancer Management and Research · doi:10.2147/cmar.s302565 · Cited by 151
Coughlan, A. M., Harmon, C., Whelan, S., O’Brien, E. C., O’Reilly, V. P., Crotty, P. L., Kelly, P., Ryan, M., Hickey, F. B., O’Farrelly, C., et al. (2016) · Stem Cells and Development · doi:10.1089/scd.2015.0289 · Cited by 134
“Functional human monocyte subsets have been identified previously in humanized NSG and Rag2 - / - IL2r g - / - mice encoding human M-CSF, IL3, GM-CSF, and TPO (MITRG mice) [33].”
Strunz, B., Bister, J., Jönsson, H., Filipovic, I., Guterstam, Y. C., Kvedaraite, E., Sleiers, N., Dumitrescu, B., Brännström, M., Lentini, A., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abb7800 · Cited by 133
“For analysis of CD39 expression on tissue-residing NK cells in the humanized mouse model, newborn MISTRG mice were transplanted with 5 × 104 human CD34+ cells and isolated from umbilical cord blood, as described previously (36), without any preconditioning by irradiation.”
BackgroundMethodInfluentialA humanized mouse model of chronic COVID-19
Sefik, E., Israelow, B., Mirza, H., Zhao, J., Qu, R., Kaffe, E., Song, E., Halene, S., Meffre, E., Kluger, Y., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01155-4 · Cited by 136
“…laboratory by combining mice generated by this lab, the laboratory of Markus Manz and Regeneron Pharmaceuticals based on the Rag2−/ − IL2rg-/−129xBalb/c background supplemented with genes for human M-CSF, IL-3, SIRP α , thrombopoietin, GM-CSF and IL6 knocked into their respective mouse loci 29,88 .”
Advanced nanomedicine and cancer: Challenges and opportunities in clinical translation
González‐Valdivieso, J., Girotti, A., Schneider, J., & Arias, F. J. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120438 · Cited by 138
Xenograft models for normal and malignant stem cells
Goyama, S., Wunderlich, M., & Mulloy, J. C. (2015) · Blood · doi:10.1182/blood-2014-11-570218 · Cited by 127
The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications
Medyouf, H. (2017) · Blood · doi:10.1182/blood-2016-11-696070 · Cited by 133
Abarrategi, A., Mian, S. A., Passaro, D., Rouault‐Pierre, K., Grey, W., & Bonnet, D. A. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20172139 · Cited by 130
“1Flv Tg(SIR PA)1Flv/J MIS TRG Rag2tm1.”
BackgroundMethodInfluentialPD-L1 blockade restores CAR T cell activity through IFN-γ-regulation of CD163+ M2 macrophages
Yamaguchi, Y., Gibson, J., Ou, K., Lopez, L. S., Ng, R. H., Leggett, N. A., Jönsson, V. D., Zarif, J. C., Lee, P. P., Wang, X., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004400 · Cited by 136
Wong, S. W., Lenzini, S. B., Cooper, M. H., Mooney, D. J., & Shin, J. (2020) · Science Advances · doi:10.1126/sciadv.aaw0158 · Cited by 126
Morton, J. J., Bird, G., Keysar, S. B., Astling, D. P., Lyons, T. R., Anderson, R. T., Glogowska, M., Estes, P., Eagles, J. R., Le, P. N., et al. (2015) · Oncogene · doi:10.1038/onc.2015.94 · Cited by 121
“Finally, the infiltration and activation of myeloid cells in xenografts has been examined in genetically modified NSG mice (17).”
BackgroundHashwah, H., Schmid, C. A., Kasser, S., Bertram, K., Stelling, A., Manz, M. G., & Mueller, A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619555114 · Cited by 121
“Most notably, however, we observed that both CREBBP–wild-type and –mutant clones engrafted in the bone marrow of MISTRG mice even without prior passaging (Fig.”
BackgroundMethodInfluentialChow, R. D.-W., & Chen, S. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.03.002 · Cited by 122
“The development and application of humanized mice [60] has helped to bridge this gap in part, particularly with regard to innate immunity, although complete humanization of the full immune system remains to be seen.”
BackgroundImproved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice
Rahmig, S., Kronstein‐Wiedemann, R., Fohgrub, J., Kronstein, N., Nevmerzhitskaya, A., Bornhäuser, M., Gassmann, M., Platz, A., Ordemann, R., Tonn, T., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.08.005 · Cited by 118
McComb, S., Aguadé-Gorgorió, J., Behrmann, L., Marovca, B., Cario, G., Eckert, C., Schrappe, M., Stanulla, M., von Stackelberg, A., Bourquin, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad2986 · Cited by 118
“Given recent improvements in humanized mouse models for studying human disease (38), the development of multicolored CRISPR-Cas9 lentiviral constructs provides an alternative to previously established in vivo functional genomic strategies (35, 39, 40), with specific focus on dissecting the complex interaction of sever…”
BackgroundHolzapfel, B. M., Wagner, F., Thibaudeau, L., Lévesque, J.-P., & Hutmacher, D. W. (2015) · Stem Cells · doi:10.1002/stem.1978 · Cited by 117
Skeletal muscle cells actively shape (auto)immune responses
Afzali, A. M., Müntefering, T., Wiendl, H., Meuth, S. G., & Ruck, T. (2018) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.12.005 · Cited by 119
Humanising the mouse genome piece by piece
Zhu, F., Nair, R., Fisher, E., & Cunningham, T. J. (2019) · Nature Communications · doi:10.1038/s41467-019-09716-7 · Cited by 114
Humanized mouse models of immunological diseases and precision medicine
Shultz, L. D., Keck, J., Burzenski, L. M., Jangalwe, S., Vaidya, S., Greiner, D. L., & Brehm, M. A. (2019) · Mammalian Genome · doi:10.1007/s00335-019-09796-2 · Cited by 116
Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia
Khawanky, N. E., Hughes, A., Yu, W., Myburgh, R., Matschulla, T., Taromi, S., Aumann, K., Clarson, J., Vinnakota, J. M., Shoumariyeh, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26683-0 · Cited by 108
Current State of Animal (Mouse) Modeling in Melanoma Research
Kuzu, O. F., Nguyen, F. D., Noory, M. A., & Sharma, A. K. (2015) · Cancer Growth and Metastasis · doi:10.4137/cgm.s21214 · Cited by 121
Humanized Rodent Models for Cancer Research
Tian, H., Lyu, Y., Yang, Y., & Hu, Z. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01696 · Cited by 116
Natural killer cell–mediated inflammation resolution is disabled in severe asthma
Duvall, M. G., Barnig, C., Cernadas, M., Ricklefs, I., Krishnamoorthy, N., Grossman, N. L., Bhakta, N. R., Fahy, J. V., Bleecker, E. R., Castro, M., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aam5446 · Cited by 109
“In future studies, use of new analytical technologies, such as CyTOF, may prove useful in obtaining additional identification from SA BAL cells, and novel humanized mouse models may enable more detailed functional analyses of innate immune cells, such as NK cells, in disease models (30).”
MethodTechniques to Study Antigen-Specific B Cell Responses
Boonyaratanakornkit, J. B., & Taylor, J. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01694 · Cited by 113
“Transgenic mice that produce humanized cytokines by knock-in replacement can be used to support human hematopoietic stem cells (104) .”
Background
Metadata
- Authors
- Rongvaux, A., Willinger, T., Martinek, J., Strowig, T., Gearty, S. V., Teichmann, L. L., Saito, Y., Marches, F., Halene, S., Palucka, A. K., Manz, M. G., & Flavell, R. A.
- Affiliations
- Yale University (US)
- University Hospital Bonn (DE)
- University Hospital Zurich (CH)
- Yale Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Manz, Markus G
- Flavell, Richard A
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-03-16
- Volume
- 32
- Issue
- 4
- Pages
- 364-372
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4017589
- OpenAlex
- W2007987850
- Cited by
- 789
- References
- 50
- Citations by year
- 2026: 48 · 2025: 52 · 2024: 61 · 2023: 69 · 2022: 70 · 2021: 94 · 2020: 70 · 2019: 67 · 2018: 65 · 2017: 62 · 2016: 62 · 2015: 46 · 2014: 23
- FWCI
- 45.61
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-12-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA140602, CA84512, P01CA084512, R01CA129350, CA129350, R01CA156689, CA156689, CA140602)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Keywords
- humanized mice, innate immune cells, myeloid cell development, natural killer cells, monocytes, macrophages, CD34+ cells, tumor xenografts
- MeSH terms
- Animals, Humans, Immunity, Innate, Killer Cells, Natural, Mice, Transgenic, Neoplasms, Experimental, Transplantation, Heterologous, Leukemic Infiltration, Myeloid Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
