Premium
Erythrocytic precursor cells show potent shear stress resistant adhesion and home to hematopoietic tissue in vivo
Author(s) -
Hintze Christian,
Ströbele Christine,
Rüster Brigitte,
Göttig Stephan,
Bugert Peter,
Seifried Erhard,
Henschler Reinhard
Publication year - 2009
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2009.02241.x
Subject(s) - homing (biology) , biology , haematopoiesis , cxcr4 , transferrin receptor , cell adhesion molecule , flow cytometry , cell adhesion , microbiology and biotechnology , immunology , hematopoietic stem cell , chemokine receptor , receptor , stem cell , chemokine , cell , inflammation , biochemistry , ecology
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. STUDY DESIGN AND 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 β 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‐1α 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. CONCLUSION: 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.