دورية أكاديمية
Robust engraftment of fetal nonhuman primate CD34-positive cells in immune-deficient mice.
| العنوان: | Robust engraftment of fetal nonhuman primate CD34-positive cells in immune-deficient mice. |
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| المؤلفون: | Little CJ; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Haynes WJ; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Huang L; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Daffada CM; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Wolfe BK; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA., Perrin E; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, Wisconsin, USA., Simpson JA; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Kropp Schmidt JA; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, Wisconsin, USA., Hinkle HM; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, Wisconsin, USA., Keding LT; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, Wisconsin, USA., Behrens RT; AIDS Vaccine Research Laboratory, University of Wisconsin - Madison, Madison, Wisconsin, USA., Evans DT; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA.; AIDS Vaccine Research Laboratory, University of Wisconsin - Madison, Madison, Wisconsin, USA., Kaufman DB; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA., Thomson JA; Morgridge Institute for Research, Madison, Wisconsin, USA., Golos TG; Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, Wisconsin, USA., Brown ME; Department of Surgery, Division of Transplantation, University of Wisconsin - Madison, Madison, Wisconsin, USA. |
| المصدر: | Journal of leukocyte biology [J Leukoc Biol] 2022 Oct; Vol. 112 (4), pp. 759-769. Date of Electronic Publication: 2022 Mar 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3673 (Electronic) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: New York : Alan R. Liss, c1984- |
| مواضيع طبية MeSH: | Granulocyte-Macrophage Colony-Stimulating Factor* , Hematopoietic Stem Cell Transplantation*, Animals ; Antigens, CD34 ; Fetal Blood ; Hematopoietic Stem Cells ; Humans ; Macaca mulatta ; Mice ; Mice, SCID ; Mice, Transgenic |
| مستخلص: | Nonhuman primates (NHPs) represent one of the most important models for preclinical studies of novel biomedical interventions. In contrast with small animal models, however, widespread utilization of NHPs is restricted by cost, logistics, and availability. Therefore, we sought to develop a translational primatized mouse model, akin to a humanized mouse, to allow for high-throughput in vivo experimentation leveraged to inform large animal immunology-based studies. We found that adult rhesus macaque mobilized blood (AMb) CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) engrafted at low but persistent levels in immune-deficient mice harboring transgenes for human (NHP cross-reactive) GM-CSF and IL3, but did not in mice with wild-type murine cytokines lacking NHP cross-reactivity. To enhance engraftment, fetal liver-derived HSPCs were selected as the infusion product based on an increased CD34 hi fraction compared with AMb and bone marrow. Coupled with cotransplantation of rhesus fetal thymic fragments beneath the mouse kidney capsule, fetal liver-derived HSPC infusion in cytokine-transgenic mice yielded robust multilineage lymphohematopoietic engraftment. The emergent immune system recapitulated that of the fetal monkey, with similar relative frequencies of lymphocyte, granulocyte, and monocyte subsets within the thymic, secondary lymphoid, and peripheral compartments. Importantly, while exhibiting a predominantly naïve phenotype, in vitro functional assays demonstrated robust cellular activation in response to nonspecific and allogenic stimuli. This primatized mouse represents a viable and translatable model for the study of hematopoietic stem cell physiology, immune development, and functional immunology in NHPs. Summary Sentence: Engraftment of rhesus macaque hematopoietic tissues in immune-deficient mice yields a robust BLT/NeoThy-type primatized mouse model for studying nonhuman primate hematopoiesis and immune function in vivo. (©2022 Society for Leukocyte Biology.) |
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| معلومات مُعتمدة: | R37 AI095098 United States AI NIAID NIH HHS; R01 AI148379 United States AI NIAID NIH HHS; P30 CA014520 United States CA NCI NIH HHS; R21 HD099576 United States HD NICHD NIH HHS; U01 HL134655 United States HL NHLBI NIH HHS; P51 OD011106 United States OD NIH HHS; U01 AI102456 United States AI NIAID NIH HHS; 75N93021C00004 United States AI NIAID NIH HHS; U01 HL134764 United States HL NHLBI NIH HHS; R01 HD103443 United States HD NICHD NIH HHS; T32 AI125231 United States AI NIAID NIH HHS; R01 AI121135 United States AI NIAID NIH HHS; R01 AI155163 United States AI NIAID NIH HHS; UL1 TR002373 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: chimerism; hematopoietic stem cells; immune system; primatized mouse; rhesus macaque |
| المشرفين على المادة: | 0 (Antigens, CD34) 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) |
| تواريخ الأحداث: | Date Created: 20220330 Date Completed: 20221003 Latest Revision: 20231002 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9522924 |
| DOI: | 10.1002/JLB.5TA0921-481RR |
| PMID: | 35352381 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1938-3673 |
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| DOI: | 10.1002/JLB.5TA0921-481RR |