Samlowski W E, Daynes R A
Proc Natl Acad Sci U S A. 1985 Apr;82(8):2508-12. doi: 10.1073/pnas.82.8.2508.
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.
骨髓移植后多能干细胞植入的效率取决于许多尚不清楚的因素。这些因素包括静脉注射的干细胞在含有促进其持续增殖所需基质成分的微环境中循环和定位的过程。我们最近发现，与凝集素花生凝集素结合的淋巴细胞在与肝去唾液酸糖蛋白受体相互作用后会被长时间隔离。由于已知骨髓干细胞也能结合花生凝集素，我们推测去唾液酸糖蛋白受体的生理功能可能会显著损害其在能够增殖的解剖部位定位的能力。在移植后的最初3 - 4小时内，采用去唾液酸糖蛋白进行竞争性抑制，以建立暂时的受体阻断。这一程序使脾脏造血集落形成增加了5至10倍。我们的研究结果表明，在小鼠骨髓移植过程中抑制肝脏去唾液酸糖蛋白受体可使干细胞更有效地定位于造血诱导微环境。植入效率的提高伴随着外周血白细胞和血小板计数更快的恢复、巨核细胞集落形成的增加以及受体存活率的提高。旨在抑制骨髓干细胞肝脏隔离的技术可能直接适用于人类骨髓移植程序。
