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Circulation of human hematopoietic cells in severe combined immunodeficient
mice after Cl2MDP-liposome-mediated macrophage depletion
CC Fraser, BP Chen, S Webb, N van Rooijen and G Kraal
Department of Histology, Medical Faculty, Free University, Amsterdam, The
Netherlands.
Intravenous injection of dichloromethylene diphosphonate (Cl2MDP)
encapsulated in liposomes results in specific elimination of macrophages in
the spleen and liver of normal mice. Severe combined immunodeficient (SCID)
mice were treated with Cl2MDP-liposomes followed by injection of human
peripheral blood leukocytes. Control SCID mice had no detectable human
cells within 72 hours as determined by fluorescence-activated cell sorting
(FACS) analysis. However, Cl2MDP- liposome-treated animals maintained a
large proportion (%) of human cells in peripheral blood and spleen for at
least 12 days. Cl2MDP- liposome-injected SCID 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 of the spleen. These results indicate that
murine mononuclear phagocytic cells may play an important role in the
clearance of human cells injected intravenously or generated endogenously
in SCID mice and that Cl2MDP-liposome-mediated macrophage depletion allows
human hematopoietic cells to circulate and survive in SCID mice, thereby
expanding the potential for studying human cellular processes in vivo.
Volume 86,
Issue 1,
pp. 183-192,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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