TY - JOUR
T1 - CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow
AU - Avigdor, Abraham
AU - Goichberg, Polina
AU - Shivtiel, Shoham
AU - Dar, Ayelet
AU - Peled, Amnon
AU - Samira, Sarit
AU - Kollet, Orit
AU - Hershkoviz, Rami
AU - Alon, Ronen
AU - Hardan, Izhar
AU - Ben-Hur, Herzl
AU - Naor, David
AU - Nagler, Amon
AU - Lapidot, Tsvee
PY - 2004/4/15
Y1 - 2004/4/15
N2 - Trafficking of human CD34+ stem/progenitor cells (HSCS/HPCs) is regulated by chemokines, cytokines, proteolytic enzymes, and adhesion molecules. We report that the adhesion receptor CD44 and its major ligand, hyaluronlc acid (HA), are essential for homing into the bone marrow (BM) and spleen of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and engraftment by human HSCs. Homing was blocked by anti-CD44 monoclonal antibodies (mAbs) or by soluble HA, and it was significantly impaired after intravenous injection of hyaluronidase. Furthermore, stromal cell-derived factor-1 (SDF-1) was found to be a rapid and potent stimulator of progenitor adhesion to immobilized HA, leading to formation of actin-containing protrusions with CD44 located at their tips. HPCs migrating on HA toward a gradient of SDF-1 acquired spread and polarized morphology with CD44 concentrating at the pseudopodia at the leading edge. These morphologic alterations were not observed when the progenitors were first exposed to anti-CD44 mAbs, demonstrating a crosstalk between CD44 and CXCR4 signaling. Unexpectedly, we found that HA is expressed on human BM sinusoidal endothelium and endosteum, the regions where SDF-1 is also abundant. Taken together, our data suggest a key role for CD44 and HA in SDF-1-dependent transendothelial migration of HSCs/HPCs and their final anchorage within specific niches of the BM.
AB - Trafficking of human CD34+ stem/progenitor cells (HSCS/HPCs) is regulated by chemokines, cytokines, proteolytic enzymes, and adhesion molecules. We report that the adhesion receptor CD44 and its major ligand, hyaluronlc acid (HA), are essential for homing into the bone marrow (BM) and spleen of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and engraftment by human HSCs. Homing was blocked by anti-CD44 monoclonal antibodies (mAbs) or by soluble HA, and it was significantly impaired after intravenous injection of hyaluronidase. Furthermore, stromal cell-derived factor-1 (SDF-1) was found to be a rapid and potent stimulator of progenitor adhesion to immobilized HA, leading to formation of actin-containing protrusions with CD44 located at their tips. HPCs migrating on HA toward a gradient of SDF-1 acquired spread and polarized morphology with CD44 concentrating at the pseudopodia at the leading edge. These morphologic alterations were not observed when the progenitors were first exposed to anti-CD44 mAbs, demonstrating a crosstalk between CD44 and CXCR4 signaling. Unexpectedly, we found that HA is expressed on human BM sinusoidal endothelium and endosteum, the regions where SDF-1 is also abundant. Taken together, our data suggest a key role for CD44 and HA in SDF-1-dependent transendothelial migration of HSCs/HPCs and their final anchorage within specific niches of the BM.
UR - http://www.scopus.com/inward/record.url?scp=11144358161&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-10-3611
DO - 10.1182/blood-2003-10-3611
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 15070674
AN - SCOPUS:11144358161
SN - 0006-4971
VL - 103
SP - 2981
EP - 2989
JO - Blood
JF - Blood
IS - 8
ER -