Adhesion Molecules Involved in Transendothelial Migration of Human Hematopoietic Progenitor Cells

Abstract

In the process of homing, CD34 + hematopoietic progenitor cells migrate across the bone marrow endothelium in response to stromal cell-derived factor (SDF)-1. To develop more efficient stem cell transplantation procedures, it is important to define the adhesion molecules involved in the homing process. Here, we identified the adhesion molecules that control the migration of primary human CD34 + cells across human bone marrow endothelial cells.Migration of CD34 + cells is enhanced across interleukin 1β prestimulated bone marrow endothelium, suggesting an important role for the endothelium in adhesion and formation of the chemotactic gradient. Under these conditions, 30-100 ng/ml SDF-1 induced a rapid and efficient migration of CD34 + cells (± 46% migration in 4 h). In contrast, 600-1,000 ng/ml SDF-1 were required for optimal migration across fibronectin-coated filters. Subsequent studies revealed that transendothelial migration of CD34+ cells is mediated by β1-and β2-integrins and PECAM-1 (CD31) but not by CD34 or E-selectin. Whereas these antibodies individually blocked migration for 25%-35%, migration was reduced by 68% when the antibodies were combined. Thus, these adhesion molecules play specific and independent roles in the transmigration process. Finally, O-glycosylated proteins appeared to play a role, since SDF-1-induced migration of CD34 + cells (treated with a glycoprotease from Pasteurella haemolytica) across endothelial cells was clearly inhibited.In conclusion, we show that efficient SDF-1-induced migration of primary human CD34 + cells across bone marrow endothelium is mediated by β1-integrins, β2-integrins, CD31 and O-glycosylated proteins.

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

“…Thus, VEGF 165 -and Ang1-mobilized bone marrow cells might migrate into the heart, differentiate into cardiomyocytes and decrease myocardial infarct size. Additionally, Voermans et al 21 indicated that efficient migration of hematopoietic progenitor CD34 + cells across the bone marrow endothelium is mediated by b 1 -integrins and b 2 -integrins. Thus, the above-supposed process might be mediated by integrins.…”

Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

“…71 In vitro studies have shown that migration of human bone marrow CD34 ϩ cells through bone marrow endothelial cell layer involves interaction of several cell surface adhesion molecules including ␤1 and ␤2 integrins, platelet endothelial cell adhesion molecule-1 (PECAM-1), and O-glycosylated proteins. 72 In vivo experiments using blocking antibodies and gene-deleted mice suggested that the integrin ␤1 chain and integrin ␣4␤1 receptor in hematopoietic stem and progenitor cells, and stromal vascular cell adhesion molecule-1 (VCAM-1), are involved in the homing and mobilization of stem cells and progenitors. [73][74][75][76] However, studies with chimeric mice with homozygous deletions of integrin ␣ chains have not settled the role of individual integrin ␣ chains in stem cell homing, and it is possible that multiple receptors are involved.…”

Characterization of a Lineage‐Negative Stem‐Progenitor Cell Population Optimized for Ex Vivo Expansion and Enriched for LTC‐IC

“…The Lin -cell subset was negative for a wide range of hematopoietic lineage markers, including CD45, glycophorin-A, CD38, CD7, CD33, CD56, CD16, CD3, and CD2. A proportion of Lin -HSPC nonetheless expressed markers: A) reflecting their immaturity status [21][22][23], such as CD133 (7.0% ± 0.8%), CD34 (14.4% ± 3.6%), intracellular CD34 (16.2% ± 0.6%), and CD164 (16.0% ± 4.1%), or B) that were involved in HSPC migration, adhesion, and homing to the bone marrow (BM) [24][25][26][27], CXCR4 (48.6% ± 4.0%), and CD162 (96.7% ± 2.0%) (Fig. 1).…”