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Compared with immunodeficient mice transplanted with human fetal thymus tissue and fetal liver\u2013derived CD34+ cells administered i.v. (Hu\/Hu mice), PI mice, which are transplanted with human fetal thymus and adult bone marrow (aBM) CD34+ cells, demonstrate reduced levels of human reconstitution. We characterized APC and APC progenitor repopulation in human immune system mice and detected significant reductions in blood, bone marrow (BM), and splenic APC populations in PI compared with Hu\/Hu mice. APC progenitors and hematopoietic stem cells (HSCs) were less abundant in aBM CD34+ cells compared with fetal liver\u2013derived CD34+ cell preparations, and this reduction in APC progenitors was reflected in the BM of PI compared with Hu\/Hu mice 14\u201320 wk posttransplant. The number of HSCs increased in PI mice compared with the originally infused BM cells and maintained functional repopulation potential, because BM from some PI mice 28 wk posttransplant generated human myeloid and lymphoid cells in secondary recipients. Moreover, long-term PI mouse BM contained functional T cell progenitors, evidenced by thymopoiesis in thymic organ cultures. Injection of aBM cells directly into the BM cavity, transgenic expression of hematopoietic cytokines, and coinfusion of human BM-derived mesenchymal stem cells synergized to enhance long-term B cell and monocyte levels in PI mice. These improvements allow a sustained time frame of 18\u201322 wk where APCs and T cells are present and greater flexibility for modeling immune disease pathogenesis and immunotherapies in PI mice.<\/jats:p>","DOI":"10.4049\/jimmunol.2100966","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T14:01:11Z","timestamp":1647871271000},"page":"1652-1663","source":"Crossref","is-referenced-by-count":6,"title":["Defects in Long-Term APC Repopulation Ability of Adult Human Bone Marrow Hematopoietic Stem Cells (HSCs) Compared with Fetal Liver HSCs"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1633-5150","authenticated-orcid":false,"given":"Grace","family":"Nauman","sequence":"first","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, Columbia University , New York, NY"},{"name":"Department of Microbiology and Immunology, Columbia University 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