Erythrocytic precursor cells show potent shear stress resistant adhesion and home to hematopoietic tissue in vivo.
BACKGROUND
Transfusion of erythropoietic precursor cells has been suggested as an alternative to conventional red blood cells. However, little is known about the fate of transfused erythrocytic precursors after they enter the bloodstream.


METHODS
Erythrocytic precursors were classified by flow cytometry into different maturation stages. Precursors were enriched using cell surface expression of CD71 and Ter119 antigens and analyzed under shear stress in a parallel plate flow chamber and after fluorescence tagging with PKH and transfusion into anemic mice.


RESULTS
We found that at all maturation stages, erythrocytic precursors expressed the adhesion receptor very late antigen (VLA)-4 with a frequency decreasing from 90% to approximately 60% during maturation. In contrast, expression of the beta(2)-integrins LFA-1 and Mac-1 and the rolling receptor P-selectin glycoprotein ligand-1 increased from 10% to 20% to approximately 50% during erythrocytic maturation. The chemokine receptor CXCR4 was expressed at low levels during differentiation stages. In vitro shear stress adhesion analysis showed that erythrocytic precursors can efficiently activate VLA-4 such that it binds its cognate ligand, vascular cell adhesion molecule (VCAM)-1. The coimmobilization of stromal cell-derived factor-1 alpha with VCAM-1 strengthened this adhesion. Transfusion of primitive (CD71+) or more mature (Ter119+) erythrocytic precursors into mice showed that both populations selectively and efficiently home to hematopoietic tissues.


CONCLUSIONS
Our results demonstrate that erythrocytic precursor cells of different maturation stages are capable of homing to hematopoietic organs. This work has implications for the development of transfusion protocols that use ex vivo expanded, but not fully matured, erythrocytic precursors from cultured stem cell populations.
Hintze
Christian
C
Institute of Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Center, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany.
Ströbele
Christine
C
Rüster
Brigitte
B
Göttig
Stephan
S
Bugert
Peter
P
Seifried
Erhard
E
Henschler
Reinhard
R
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D051379:Mice; D011990:Receptors, Transferrin / Q000378:metabolism; D033081:Shear Strength; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; C068126:CD71 antigen; D039041:Integrin alpha4beta1; D011990:Receptors, Transferrin; D019010:Vascular Cell Adhesion Molecule-1