title: Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity.
abstract: Human embryonic stem cells (hESCs) provide a unique resource to analyze early stages of human hematopoiesis. However, little is known about the ability to use hESCs to evaluate lymphocyte development. In the present study, we use a two-step culture method to demonstrate efficient generation of functional NK cells from hESCs. The CD56(+)CD45(+) hESC-derived lymphocytes express inhibitory and activating receptors typical of mature NK cells, including killer cell Ig-like receptors, natural cytotoxicity receptors, and CD16. Limiting dilution analysis suggests that these cells can be produced from hESC-derived hemopoietic progenitors at a clonal frequency similar to CD34(+) cells isolated from cord blood. The hESC-derived NK cells acquire the ability to lyse human tumor cells by both direct cell-mediated cytotoxicity and Ab-dependent cellular cytotoxicity. Additionally, activated hESC-derived NK cells up-regulate cytokine production. hESC-derived lymphoid progenitors provide a novel means to characterize specific cellular and molecular mechanisms that lead to development of specific human lymphocyte populations. These cells may also provide a source for innovative cellular immune therapies.
authors.affiliation: Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Petter S
authors.initials: PS
authors.lastname: Woll
authors.forename: Colin H
authors.initials: CH
authors.lastname: Martin
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000502:physiology; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D016207:Cytokines; D011971:Receptors, Immunologic