Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rγKO mice.
نویسندگان
چکیده
Although physiological development of human lymphoid subsets has become well documented in humanized mice, in vivo development of human myeloid subsets in a xenotransplantation setting has remained unevaluated. Therefore, we investigated in vivo differentiation and function of human myeloid subsets in NOD/SCID/IL2rγ(null) (NSG) mouse recipients transplanted with purified lineage(-)CD34(+)CD38(-) cord blood hematopoietic stem cells. At 4-6 mo posttransplantation, we identified the development of human neutrophils, basophils, mast cells, monocytes, and conventional and plasmacytoid dendritic cells in the recipient hematopoietic organs. The tissue distribution and morphology of these human myeloid cells were similar to those identified in humans. After cytokine stimulation in vitro, phosphorylation of STAT molecules was observed in neutrophils and monocytes. In vivo administration of human G-CSF resulted in the recruitment of human myeloid cells into the recipient circulation. Flow cytometry and confocal imaging demonstrated that human bone marrow monocytes and alveolar macrophages in the recipients displayed intact phagocytic function. Human bone marrow-derived monocytes/macrophages were further confirmed to exhibit phagocytosis and killing of Salmonella typhimurium upon IFN-γ stimulation. These findings demonstrate the development of mature and functionally intact human myeloid subsets in vivo in the NSG recipients. In vivo human myelopoiesis established in the NSG humanized mouse system may facilitate the investigation of human myeloid cell biology including in vivo analyses of infectious diseases and therapeutic interventions.
منابع مشابه
Development of Mature and Functional Human Myeloid Subsets in Hematopoietic Stem Cell-Engrafted NOD/SCID/IL2rgKO Mice
متن کامل
Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors.
Distinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develop human myeloid and plasmacytoid DCs. The skin displays immature DCs expressin...
متن کاملDasatinib induces complete remission in a patient with primary cerebral involvement of B-cell chronic lymphocytic leukemia failing chemotherapy.
1. Notta F, Doulatov S, Dick JE. Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients. Blood. 2010; 115(18):3704-3707. 2. Shultz LD, Lyons BL, Burzenski LM, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477-6489. 3. Agli...
متن کاملTransduction of human NOD/SCID-repopulating cells with both lymphoid and myeloid potential by foamy virus vectors.
The efficiency of gene transfer into human hematopoietic stem cells by oncoretroviral vectors is too low for effective gene therapy of most hematologic diseases. Retroviral vectors based on the nonpathogenic foamy viruses (FV) are an alternative gene-transfer system. In this study, human umbilical cord blood CD34(+) cells were transduced with FV vectors by a single 10-h exposure to vector stock...
متن کاملEngraftment and development of human CD34(+)-enriched cells from umbilical cord blood in NOD/LtSz-scid/scid mice.
Understanding the repopulating characteristics of human hematopoietic stem/progenitor cell fractions is crucial for predicting their performance after transplant into high-risk patients following high-dose therapy. We report that human umbilical cord blood cells, 78% to 100% of which express the hematopoietic progenitor cell surface marker CD34, can consistently engraft, develop, and proliferat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 188 12 شماره
صفحات -
تاریخ انتشار 2012