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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 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 Citation Map 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 Hematopoiesis and Stem Cells Red Cells Transfusion Medicine Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Biologic properties and enucleation of red blood cells from human embryonic stem cells Shi-Jiang Lu*,1, Qiang Feng*,1, Jennifer S. Park*,1, Loyda Vida2, Bao-Shiang Lee3, Michael Strausbauch4, Peter J. Wettstein4, George R. Honig2, and Robert Lanza1 1 Advanced Cell Technology, Worcester, MA; 2 Department of Pediatrics, University of Illinois at Chicago; 3 Protein Research Laboratory, Research Resources Center, University of Illinois at Chicago; and 4 Departments of Surgery and Immunology, Mayo Clinic, Rochester, MN 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 (1010-1011 cells/6-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable with normal red blood cells 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 β-globin chain on further maturation in vitro. Polymerase chain reaction and globin chain specific immunofluorescent analysis showed that the cells increased expression of β-globin (from 0% to > 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 more than 60% of the cells generating red blood cells with a diameter of approximately 6 to 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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