Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity.
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.
Woll
Petter S
PS
Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Martin
Colin H
CH
Miller
Jeffrey S
JS
Kaufman
Dan S
DS
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
D016207:Cytokines; D011971:Receptors, Immunologic