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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4475-4484. Prepublished online as a Blood First Edition Paper on August 19, 2008; DOI 10.1182/blood-2008-05-157198. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-05-157198v1 112/12/4475    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lu, S.-J. Articles by Lanza, R. Search for Related Content PubMed PubMed Citation Articles by Lu, S.-J. Articles by Lanza, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 22, 2008 Accepted August 7, 2008 Biological properties and enucleation of red blood cells from human embryonic stem cells Shi-Jiang Lu, Qiang Feng, Jennifer S. Park, Loyda Vida, Bao-Shiang Lee, Michael Strausbauch, Peter J. Wettstein, George R. Honig, and Robert Lanza* R&D, Advanced Cell Technology, Worcester, MA, United States Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, United States Protein Research Laboratory, University of Illinois at Chicago, Chicago, IL, United States Departments of Surgery and Immunology, Mayo Clinic, Rochester, MN, United States * Corresponding author; email: rlanza{at}advancedcell.com. Human erythropoiesis is a complex multistep process that involves the differentiation of early erythroid progenitors to mature erythrocytes. Here we show that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (1010 to 1011 cells/six-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable to normal red blood cells (RBCs) and respond to changes in pH and 2,3-diphosphoglyerate. Although these cells mainly expressed fetal and embryonic globins, they also possessed the capacity to express the adult definitive -globin chain upon further maturation in vitro. PCR and globin chain specific immunofluorescent analysis showed that the cells increased expression of -globin (increased from 0% to over 16%) after in vitro culture. Importantly, the cells underwent multiple maturation events, including a progressive decrease in size, increase in glycophorin A expression, and chromatin and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to over 60% of the cells generating RBCs with a diameter of approximately 6-8 µm. The results show that it is feasible to differentiate and mature hESCs into functional oxygen-carrying erythrocytes on a large scale. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Toward the manufacture of red blood cells? Eric E. Bouhassira Blood 2008 112: 4362-4363. [Full Text] [PDF] This article has been cited by other articles: D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF]

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