Modulating erythrocyte chimerism in a mouse model of pyruvate kinase deficiency

Author:

Richard Robert E.1,Weinreich Michael1,Chang Kai-Hsin1,Ieremia Jessica1,Stevenson Mary M.1,Blau C. Anthony1

Affiliation:

1. From the Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and the Montreal General Hospital Research Institute, Quebec, Canada.

Abstract

Abstract In vivo selection may provide a means to increase the relative number of cells of donor origin in recipients with hemopoietic chimerism. We have tested whether in vivo selection using chemical inducers of dimerization (CIDs) can direct the expansion of transduced normal donor erythrocytes in recipients with chimerism using a mouse model of pyruvate kinase deficiency. Marrow cells from normal CBA/N mice were transduced with a vector (F36VmplGFP) that promotes cell growth in the presence of CIDs. Transduced cells were then transplanted into minimally conditioned, pyruvate kinase-deficient recipients (CBA-Pk-1slc/Pk-1slc) to establish stable chimerism. CID administration resulted in expansion of normal donor erythrocytes and improvement of the anemia. The preferential expansion of normal erythrocytes also resulted in a decrease in erythropoietin levels, reducing the drive for production of pyruvate kinase-deficient red blood cells. CID-mediated expansion of genetically modified erythrocytes could prove a useful adjunct to transplantation methods that achieve erythroid chimerism. (Blood. 2004;103:4432-4439)

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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