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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2142-2150
Behavior and Therapeutic Efficacy of  -Glucuronidase-Positive
Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type
VII
Brian J. Freeman,
Marie S. Roberts,
Carole A. Vogler,
Andrew Nicholes,
A. Alex Hofling, and
Mark S. Sands
From the Department of Internal Medicine, Washington University
School of Medicine, St Louis, MO; and the Department of Pathology, St
Louis University School of Medicine, St Louis, MO.
Bone marrow transplantation (BMT) is relatively effective for the
treatment of lysosomal storage diseases. To better understand the
contribution of specific hematopoietic lineages to the efficacy of BMT,
we transplanted  -glucuronidase-positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into
syngeneic recipients with mucopolysaccharidosis type VII (MPS VII).
Cell surface marking studies indicate that the bone marrow-derived
cells are less mature than the peritoneal macrophages. However, both
cell types retain the ability to home to tissues rich in cells of the
reticuloendothelial system after intravenous injection into MPS VII
mice. The half-life of both types of donor macrophages is approximately
7 days, and some cells persist for at least 30 days. In several
tissues, therapeutic levels of -glucuronidase are present, and
histopathologic analysis demonstrates that lysosomal storage is
dramatically reduced in the liver and spleen. Macrophages intravenously
injected into newborn MPS VII mice localize to the same tissues as
adult mice but are also observed in the meninges and parenchyma of the
brain. These data suggest that macrophages play a significant role in
the therapeutic efficacy of BMT for lysosomal storage diseases and may
have implications for treatments such as gene therapy.
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