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An In Vitro Model of Human Red Blood Cell Production From
Hematopoietic Progenitor Cells
Punam Malik,
Timothy C. Fisher,
Lora L.W. Barsky,
Licheng Zeng,
Parvin Izadi,
Alan L. Hiti,
Kenneth I. Weinberg,
Thomas D. Coates,
Herbert J. Meiselman, and
Donald B. Kohn
From the Divisions of Research Immunology/Bone Marrow Transplantation
and Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles,
CA; and the Departments of Physiology and Biophysics and of Pathology,
University of Southern California School of Medicine, Los Angeles, CA.
Hemoglobinopathies, such as  -thalassemias and sickle cell anemia
(SCA), are among the most common inherited gene defects. Novel models of human erythropoiesis that result in terminally differentiated red blood cells (RBCs) would be able to address the
pathophysiological abnormalities in erythrocytes in congenital RBC
disorders and to test the potential of reversing these problems by gene
therapy. We have developed an in vitro model of production of human
RBCs from normal CD34+ hematopoietic progenitor cells,
using recombinant growth factors to promote terminal RBC
differentiation. Enucleated RBCs were then isolated to a pure
population by flow cytometry in sufficient numbers for physiological
studies. Morphologically, the RBCs derived in vitro ranged from early
polylobulated forms, resembling normal reticulocytes to smooth
biconcave discocytes. The hemoglobin pattern in the in vitro-derived
RBCs mimicked the in vivo adult or postnatal pattern of -globin
production, with negligible  -globin synthesis. To test the gene
therapy potential using this model, CD34+ cells were
genetically marked with a retroviral vector carrying a cell-surface
reporter. Gene transfer into CD34+ cells followed by
erythroid differentiation resulted in expression of the marker gene on
the surface of the enucleated RBC progeny. This model of human
erythropoiesis will allow studies on pathophysiology of congenital RBC
disorders and test effective therapeutic strategies.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2664-2671
© 1998 by The American Society of Hematology.
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