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Abstracts: ASAIO Bioengineering/tissue Engineering Abstracts

EFFECTS OF LIPOSOME-ENCAPSULATED HEMOGLOBIN (TRM645) ON HUMAN IMMUNE SYSTEM: EVALUATION IN IMMUNODEFFICIENT MICE RECONSTITUTED WITH HUMAN STEM CELLS

Kawaguchi, Akira T1; Kametani, Yoshie1; Haida, Munetaka1; Sakai, Akiko1; Habu, Sonoko1

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Background.

Safety evaluation in animals sometimes overlooks untoward effects in humans. Liposome-encapsulated hemoglobin (TRM645) is tested in mice reconstituted with human immune system as a preclinical safety evaluation.

Methods.

Newly established immunodeficient mice (NOG) were transfused with 2x105 hematopoietic stem cells isolated from human cord blood. In those mice, changes in immunocompetent cells in peripheral blood, spleen and bone marrow were examined before and 2 days after 1% body weight intravenous administration of TRM645 (n=4), empty liposome (n=4), and phosphate buffered saline (n=4) using immunohistochemical and flow-cytometrical techniques.

Results.

Although there was an increase in numbers of human CD4+ (helper T) cells, CD8+ (suppressor T) cells and CD19+ (B) cells in the spleen of mice receiving liposome (TRM645 or empty liposome) as compared to mice receiving saline, these cells were all in resting state (CD25-). Cellularity, distribution and maturation of these human cells in bone marrow or peripheral blood were comparable among the groups.

Conclusion.

The increase of resting human lymphocytes in mouse spleen receiving liposome may suggest a natural metabolic pathway where liposome is captured and degraded by the reticuloendothelial system. In a short-term there was no apparent untoward effect of TRM645 per se as these mice are all active and healthy. Studies on effects of repeated administration of TRM645 on long-term, and on active immunization in the “human mice” are underway.

Copyright © 2005 by the American Society for Artificial Internal Organs