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 Blood, 11 June 2009, Vol. 113, No. 24, pp. 6094-6101.
Prepublished online as a Blood First Edition Paper on April 13, 2009; DOI 10.1182/blood-2008-06-165225.

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Submitted June 25, 2008
Accepted April 6, 2009

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

Petter S. Woll, Bartosz Grzywacz, Xinghui Tian, Rebecca K. Marcus, David A. Knorr, Michael R. Verneris, and Dan S. Kaufman*

Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, MN, United States
Departments of Pediatrics and Medicine, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, United States

* Corresponding author; email: kaufm020{at}umn.edu.

Natural killer (NK) cells serve as important effectors for anti-tumor 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 anti-tumor response. Using bioluminescent imaging we now demonstrate 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 as compared to NK cells derived from umbilical cord blood (UCB). Phenotypic analysis demonstrates the hESC-derived NK cells are uniformly CD94+CD117low/-, a 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 anti-tumor immunotherapy.


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