Biologic 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, Robert Lanza

Research output: Contribution to journalArticle

224 Scopus citations

Abstract

Human erythropoiesis is a complex multi-step 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 (10 10-10 11 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.

Original languageEnglish (US)
Pages (from-to)4475-4484
Number of pages10
JournalBlood
Volume112
Issue number12
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Lu, S. J., Feng, Q., Park, J. S., Vida, L., Lee, B. S., Strausbauch, M., Wettstein, P. J., Honig, G. R., & Lanza, R. (2008). Biologic properties and enucleation of red blood cells from human embryonic stem cells. Blood, 112(12), 4475-4484. https://doi.org/10.1182/blood-2008-05-157198