CIRCULATION OF HUMAN HEMATOPOIETIC-CELLS IN SEVERE COMBINED IMMUNODEFICIENT MICE AFTER CL(2)MDP-LIPOSOME-MEDIATED MACROPHAGE DEPLETION

Intravenous injection of dichloromethylene diphosphonate (Cl(2)MDP) en capsulated in liposomes results in specific elimination of macrophages in the spleen and liver of normal mice,Severe combined immunodeficien t (SCID) mice were treated with Cl(2)MDP-liposomes followed by injecti on of human peripheral blood leukocytes, Control SCID mice had no dete ctable human cells within 72 hours as determined by fluorescence-activ ated cell sorting (FAGS) analysis. However, Cl(2)MDP-liposome-treated animals maintained a large proportion (%) of human cells in peripheral blood and spleen for at least 12 days. Cl(2)MDP-liposome-injected SCI D mice that had previously been implanted with human fetal thymus and liver showed a transient increase in human cell content in peripheral blood, and an accumulation of human cells specific to the white pulp o f the spleen, These results indicate that murine mononuclear phagocyti c cells may play an important role in the clearance of human cells inj ected intravenously or generated endogenously in SCID mice and that Cl (2)MDP-liposome-mediated macrophage depletion allows human hematopoiet ic cells to circulate and survive in SCID mice, thereby expanding the potential for studying human cellular processes in vivo. (C) 1995 by T he American Society of Hematology.