Clinical Epidemiology and Ageing

In vitro generated Rh(null) red cells recapitulate the in vivo deficiency: a model for rare blood group phenotypes and erythroid membrane disorders.

Cambot M, Mazurier C, Canoui-Poitrine F, Hebert N, Picot J, Clay D, Picard V, Ripoche P, Douay L, Dubart-Kupperschmitt A, Cartron J-P Am J Hematol. 2013;88(5):343-9.

Lentiviral modification combined with ex vivo erythroid differentiation was used to stably inhibit RhAG expression, a critical component of the Rh(rhesus) membrane complex defective in the Rh(null) syndrome. The cultured red cells generated recapitulate the major alterations of native Rh(null) cells regarding antigen expression, membrane deformability, and gas transport function, providing the proof of principle for their use as model of Rh(null) syndrome and to investigate Rh complex biogenesis in human primary erythroid cells. Using this model, we were able to reveal for the first time that RhAG extinction alone is sufficient to explain ICAM-4 and CD47 loss observed on native Rh(null) RBCs. Together with the effects of RhAG forced expression in Rh(null) progenitors, this strongly strengthens the hypothesis that RhAG is critical to Rh complex formation. The strategy is also promising for diagnosis purpose in order to overcome the supply from rare blood donors and is applicable to other erythroid defects and rare phenotypes, providing models to dissect membrane biogenesis of multicomplex proteins in erythroid cells, with potential clinical applications in transfusion medicine.

MeSH terms: Adult Stem Cells; Anemia, Hemolytic, Congenital; Anemia, Hypoplastic, Congenital; Blood Proteins; CD47 Antigen; Cell Adhesion Molecules; Cell Differentiation; Cell Line; Cells, Cultured; Erythroid Cells; Erythroid Precursor Cells; Female; Fetal Blood; Fetal Stem Cells; Genetic Diseases, Inborn; Humans; Membrane Glycoproteins; Porphyria, Erythropoietic; Pregnancy; Reticulocytes; Rh-Hr Blood-Group System; RNA Interference; RNA, Small Interfering
DOI: 10.1002/ajh.23414

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