Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity

• Published in: Blood Vol. 113; no. 24; pp. 6094 - 6101
• Main Authors: Woll, Petter S., Grzywacz, Bartosz, Tian, Xinghui, Marcus, Rebecca K., Knorr, David A., Verneris, Michael R., Kaufman, Dan S.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 11.06.2009; Americain Society of Hematology; American Society of Hematology
• Series: Hematopoiesis and Stem Cells
• Subjects: Animals; Biological and medical sciences; Bone Marrow - immunology; Cell Differentiation; Cells, Cultured; Embryonic Stem Cells - cytology; Fetal Blood - cytology; Flow Cytometry; Hematologic and hematopoietic diseases; Hematopoiesis and Stem Cells; Humans; Kidney Neoplasms - immunology; Kidney Neoplasms - prevention & control; Kidney Neoplasms - secondary; Killer Cells, Natural - immunology; Leukemia, Experimental - immunology; Leukemia, Experimental - pathology; Leukemia, Experimental - prevention & control; Liver Neoplasms - immunology; Liver Neoplasms - prevention & control; Liver Neoplasms - secondary; Lung Neoplasms - immunology; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Stromal Cells - immunology; Antineoplastic agent; Natural killer cell; Human; In vivo; Hematology; Cell population; Embryonic cell; Stem cell; Biological activity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-06-165225

Natural killer (NK) cells serve as important effectors for antitumor immunity, and CD56+CD45+ NK cells can be routinely derived from human embryonic stem cells (hESCs). However, little is know about the ability of hESC-derived NK cells to mediate an effective in vivo antitumor response. Using bioluminescent imaging, we now demonstrate that H9 line hESC-derived NK cells mediate effective clearance of human tumor cells in vivo. In addition to increased in vitro killing of diverse tumor targets, the in vivo tumor clearance by H9 hESC-derived NK cells was more effective compared with NK cells derived from umbilical cord blood (UCB). Phenotypic analysis demonstrates the hESC-derived NK cells are uniformly CD94+CD117low/−, an NK-cell population characterized by potent cytolytic activity and thus more competent to mediate tumor clearance. These studies demonstrate that hESCs provide an important model to study human lymphocyte development and may serve as a novel source for antitumor immunotherapy.