Bone marrow engraftment efficiency is enhanced by competitive inhibition of the hepatic asialoglycoprotein receptor

Abstract

The efficiency of pluripotent stem cell engraftment following bone marrow transplantation is predicated upon many poorly understood factors. These include the processes by which intravenously injected stem cells circulate and localize in microenvironments that contain the stromal elements necessary to facilitate their continued proliferation. We have recently established that lymphoid cells that bind the lectin peanut agglutinin are subject to prolonged sequestration following their interaction with the hepatic asialoglycoprotein receptor. Since bone marrow stem cells are also known to bind peanut agglutinin, we hypothesized that the physiologic function of the asialoglycoprotein receptor might significantly impair their ability to localize in anatomic sites where they are able to proliferate. Competitive inhibition with asialoglycoproteins was employed to establish a temporary receptor blockade during the initial 3-4 hr after transplantation. This procedure resulted in a 5- to 10-fold increase in splenic hematopoietic colony formation. Our findings suggest that inhibition of the liver asialoglycoprotein receptor during murine bone marrow transplantation results in more efficient stem cell localization to hematopoietic-inducing microenvironments. This enhancement in engraftment efficiency was paralleled by a more rapid recovery of peripheral blood leukocyte and platelet counts, an increase in megakaryocytic colony formation, as well as increased recipient survival. Techniques designed to inhibit the liver sequestration of bone marrow stem cells may have direct applicability to human bone marrow transplantation procedures.